Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes.[1] Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain.[1] As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.[11]

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Wiki: Acute B-cell lymphoblastic leukemia

    A lymphoid leukemia that occurs when a hematopoietic stem cell undergoes malignant transformation into a primitive, undifferentiated cell with abnormal longevity producing large numbers of white blood cells to be produced and enter the blood stream.

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DiseaseOntology: Acute leukemia

    A acute leukemia that is characterized by over production of lymphoblasts.

Reference
DiseaseOntology: Acute lymphoblastic leukemia

    Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li¨CFraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically Acute lymphoblastic leukemia based on blood tests and bone marrow examination. Acute lymphoblastic leukemia is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy typically over a number of years. Treatment usually also includes intrathecal chemotherapy since systemic chemotherapy can have limited penetration into the central nervous system and the central nervous system is a common site for relapse of acute lymphoblastic leukemia. Treatment can also include radiation therapy if spread to the brain has occurred. Stem cell transplantation may be used if the disease recurs following standard treatment. Additional treatments such as Chimeric antigen receptor T cell immunotherapy are being used and further studied. Acute lymphoblastic leukemia affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. Acute lymphoblastic leukemia is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%).

Reference
Wiki: Acute lymphocytic leukemia

    Acute monocytic leukemia (AMoL, or AML-M5) is a type of acute myeloid leukemia. In AML-M5 >80% of the leukemic cells are of monocytic lineage. This cancer is characterized by a dominance of monocytes in the bone marrow. There is an overproduction of monocytes that the body does not need in the periphery. These overproduced monocytes interfere with normal immune cell production which causes many health complications for the affected individual.

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Wiki: Acute monocytic leukemia

    Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production.[1] Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection.[1] Occasionally, spread may occur to the brain, skin, or gums.[1] As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.[1]

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Wiki: Acute myelogenous leukemia

    A myeloid leukemia that is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.

Reference
DiseaseOntology: Acute myeloid leukemia

    Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production.[1] Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection.[1] Occasionally, spread may occur to the brain, skin, or gums.[1] As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.[1]

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Wiki: Acute myeloid leukemia/acute myelogenous leukemia

    Acute myelomonocytic leukemia (AMML) is a form of acute myeloid leukemia that involves a proliferation of CFU-GM myeloblasts and monoblasts. AMML occurs with a rapid increase amount in white blood cell count and is defined by more than 20% of myeloblast in the bone marrow. It is classified under "M4" in the French-American-British classification (FAB).[1] It is classified under "AML, not otherwise classified" in the WHO classification.[2]

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Wiki: Acute myelomonocytic leukemia

    An acute myeloid leukemia characterized by accumulation of promyelocytes in the bone marrow and by a translocation between chromosomes 15 and 17.

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DiseaseOntology: Acute promyelocytic leukemia

    A T-cell acute leukemia that results_in abnormal increase of lymphocytes, derives_from T-cells, has_material_basis_in Human T-lymphotropic virus 1 (HTLV-1), which is transmitted_by sexual contact, transmitted_by contaminated needles used by intravenous-drug users, and transmitted_by breast feeding. The infection results_in_formation_of skin lesions.

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DiseaseOntology: Adult T-cell leukemia/lymphoma

    Congenital afibrinogenemia is a rare, genetically inherited blood fibrinogen disorder in which the blood does not clot normally due to the lack of fibrinogen, a blood protein necessary for coagulation. This disorder is autosomal recessive, meaning that two unaffected parents can have a child with the disorder. The lack of fibrinogen expresses itself with excessive and, at times, uncontrollable bleeding.

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Wiki: Afibrinogenemia

    Hypogammaglobulinemia is an immune system disorder in which not enough gamma globulins are produced in the blood (thus hypo- + gamma + globulin + -emia). This results in a lower antibody count, which impairs the immune system, increasing risk of infection. Hypogammaglobulinemia may result from a variety of primary genetic immune system defects, such as common variable immunodeficiency, or it may be caused by secondary effects such as medication, blood cancer, or poor nutrition, or loss of gamma globulins in urine, as in nonselective glomerular proteinuria. Patients with hypogammaglobulinemia have reduced immune function; important considerations include avoiding use of live vaccines, and take precautionary measures when traveling to regions with endemic disease or poor sanitation such as receiving immunizations, taking antibiotics abroad, drinking only safe or boiled water, arranging appropriate medical cover in advance of travel, and ensuring continuation of any immunoglobulin infusions needed.

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Wiki: Agammaglobulinemia

    A hematopoietic system disease that is characterized by a decrease in the normal number of red blood cells.

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DiseaseOntology: Anemia

    Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 464-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. ¦Á-Antithrombin is the dominant form of antithrombin found in blood plasma and has an oligosaccharide occupying each of its four glycosylation sites. A single glycosylation site remains consistently un-occupied in the minor form of antithrombin, ¦Â-antithrombin. Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to factor IIa (thrombin) and factor Xa.

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Wiki: Antithrombin deficiency

    Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Aplastic anemia is associated with cancer and various cancer syndromes. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets. It occurs most frequently in people in their teens and twenties but is also common among the elderly. It can be caused by heredity, immune disease, or exposure to chemicals, drugs, or radiation. However, in about half of cases, the cause is unknown. Aplastic anemia can be definitively diagnosed by bone marrow biopsy. Normal bone marrow has 30¨C70% blood stem cells, but in aplastic anemia, these cells are mostly gone and are replaced by fat. First-line treatment for aplastic anemia consists of immunosuppressive drugs¡ªtypically either anti-lymphocyte globulin or anti-thymocyte globulin¡ªcombined with corticosteroids, chemotherapy, and ciclosporin. Hematopoietic stem cell transplantation is also used, especially for patients under 30 years of age with a related, matched marrow donor. Aplastic anemia is known to have caused the deaths of Marie Curie, Eleanor Roosevelt, Luana Reyes, and Molly Holzschlag.

Reference
Wiki: Aplastic anemia

    Atypical chronic myeloid leukemia (aCML) is a type of leukemia. It is a heterogeneous disorder belonging to the group of myelodysplastic/myeloproliferative (MDS/MPN) syndromes. In aCML many clinical features (splenomegaly, myeloid predominance in the bone marrow with some dysplastic features but without a differentiation block) and laboratory abnormalities (myeloid proliferation, low leukocyte alkaline phosphatase values) suggest the diagnosis of chronic myelogenous leukemia (CML). However the lack of the pathognomonic Philadelphia chromosome and of the resulting BCR-ABL1 fusion point to a different pathogenetic process. Since no specific recurrent genomic or karyotypic abnormalities have been identified in aCML, the molecular pathogenesis of this disease has remained elusive and the outcome dismal (median survival 37 months) with no improvement over the last 20 years. This sharply contrasts with the outcome for CML, for which the prognosis was dramatically improved by the development of imatinib as a specific inhibitor of the BCR-ABL protein and in particular for CML. In 2012 SETBP1 was identified as a novel oncogene in aCML; specific somatic mutations of this gene were discovered in people with aCML and related diseases. These mutations, which are identical to the ones present in SGS as germline mutations, impair the degradation of SETBP1 and therefore cause increased cellular levels of the protein.

Reference
Wiki: Atypical chronic myeloid leukemia

    Hemolytic¨Curemic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney injury (previously called acute renal failure), and low platelets. Initial symptoms typically include bloody diarrhea, fever, vomiting, and weakness. Kidney problems and low platelets then occur as the diarrhea progresses. Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. Adults, especially the elderly, may present a more complicated presentation. Complications may include neurological problems and heart failure. Most cases occur after infectious diarrhea due to a specific type of E. coli called O157:H7. Other causes include S. pneumoniae, Shigella, Salmonella, and certain medications. The underlying mechanism typically involves the production of Shiga toxin by the bacteria. Atypical hemolytic uremic syndrome (aHUS) is often due to a genetic mutation and presents differently. However, both can lead to widespread inflammation and multiple blood clots in small blood vessels, a condition known as thrombotic microangiopathy. Treatment involves supportive care and may include dialysis, steroids, blood transfusions, or plasmapheresis. About 1.5 per 100,000 people are affected per year. Less than 5% of those with the condition die. Of the remainder, up to 25% have ongoing kidney problems. HUS was first defined as a syndrome in 1955.

Reference
Wiki: Atypical hemolytic-uremic syndrome

    Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li¨CFraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically Acute lymphoblastic leukemia based on blood tests and bone marrow examination. Acute lymphoblastic leukemia is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy typically over a number of years. Treatment usually also includes intrathecal chemotherapy since systemic chemotherapy can have limited penetration into the central nervous system and the central nervous system is a common site for relapse of acute lymphoblastic leukemia. Treatment can also include radiation therapy if spread to the brain has occurred. Stem cell transplantation may be used if the disease recurs following standard treatment. Additional treatments such as Chimeric antigen receptor T cell immunotherapy are being used and further studied. Acute lymphoblastic leukemia affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. Acute lymphoblastic leukemia is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%).

Reference
Wiki: B-cell acute lymphoblastic leukemia

    Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years. Risk factors include having a family history of the disease, with 10% of those who develop CLL having such ancestry. Exposure to Agent Orange, certain insecticides, sun exposure, exposure to hepatitis C virus, and common infections are also considered risk factors. CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. CLL is divided into two main types: Those with a mutated IGHV gene Those without. Diagnosis is typically based on blood tests finding high numbers of mature lymphocytes and smudge cells. Early-stage CLL in asymptomatic cases responds better to careful observation, as there is no evidence that early intervention treatment can alter the course of the disease. Immune defects occur early in the course of CLL and these increase the risk of developing serious infection, which should be treated appropriately with antibiotics. In those with significant symptoms, chemotherapy, immunotherapy, or chemoimmunotherapy may be used. Depending on the individual's age, physical condition, and whether they have the del(17p) or TP53 mutation, different first line treatments may be offered. As of 2021, BTK inhibitors such as ibrutinib and acalabrutinib are often recommended for first line treatment of CLL. The medications fludarabine, cyclophosphamide, and rituximab were previously the initial treatment in those who are otherwise healthy. CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. In 2021, the estimated incidence of CLL in the United States is 21,250 new cases and 4,320 deaths. The disease most commonly occurs in people over the age of 65, due to the accumulation of genetic mutations that occur over time. Men are diagnosed around twice as often as women (6.8 to 3.5 ratio). It is much less common in people from Asia. Five-year survival following diagnosis is approximately 83% in the United States. It represents less than 1% of deaths from cancer.

Reference
Wiki: B-cell chronic lymphocytic leukemia

    Tumor antigen is an antigenic substance produced in tumor cells, i.e., it triggers an immune response in the host. Tumor antigens are useful tumor markers in identifying tumor cells with diagnostic tests and are potential candidates for use in cancer therapy. The field of cancer immunology studies such topics.

Reference
Wiki: B-cell tumor

    Acute basophilic leukemia is a rare form of acute myeloid leukemia where blasts are accompanied by abnormal basophils in all stages of differentiation. It would most likely be classified as M0 without electron microscopic confirmation of basophil lineage.

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Wiki: Basophilic leukemia

    Bernard-Soulier syndrome is an autosomal recessive bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor (VWF; 613160) receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5 (173511).

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OMIM: Bernard soulier syndrome

    A thalassemia characterized by the reduced or absent synthesis of the beta globin chains of hemoglobin.

Reference
DiseaseOntology: Beta thalassemia

    Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes (neutrophils, eosinophils and basophils) and their precursors is found; characteristic increase in basophils is clinically relevant. It is a type of myeloproliferative neoplasm associated with a characteristic chromosomal translocation called the Philadelphia chromosome. CML is largely treated with targeted drugs called tyrosine-kinase inhibitors (TKIs) which have led to dramatically improved long-term survival rates since 2001. These drugs have revolutionized treatment of this disease and allow most patients to have a good quality of life when compared to the former chemotherapy drugs. In Western countries, CML accounts for 15¨C25% of all adult leukemias and 14% of leukemias overall (including the pediatric population, where CML is less common).

Reference
Wiki: Blast crisis chronic myeloid leukemia

    Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur spontaneously or following an injury or medical and dental procedures. Coagulopathies are sometimes erroneously referred to as "clotting disorders", but a clotting disorder is the opposite, defined as a predisposition to excessive clot formation (thrombus), also known as a hypercoagulable state or thrombophilia.

Reference
Wiki: Bleeding disorder

    Bone marrow failure occurs in individuals who produce an insufficient amount of red blood cells, white blood cells or platelets. Red blood cells transport oxygen to be distributed throughout the body's tissue. White blood cells fight off infections that enter the body. Bone marrow also contains platelets, which trigger clotting, and thus help stop the blood flow when a wound occurs.

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Wiki: Bone marrow failure syndrome

    A congenital hemolytic anemia characterized by mild congenital hemolytic anemia without morphologic red cell abnormalities that has_material_basis_in hemizygous mutation in the ATP11C gene on chromosome Xq27.1.

Reference
DiseaseOntology: CD59-mediated hemolytic anemia

    Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years. Risk factors include having a family history of the disease, with 10% of those who develop CLL having such ancestry. Exposure to Agent Orange, certain insecticides, sun exposure, exposure to hepatitis C virus, and common infections are also considered risk factors. CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. CLL is divided into two main types: Those with a mutated IGHV gene Those without. Diagnosis is typically based on blood tests finding high numbers of mature lymphocytes and smudge cells. Early-stage CLL in asymptomatic cases responds better to careful observation, as there is no evidence that early intervention treatment can alter the course of the disease. Immune defects occur early in the course of CLL and these increase the risk of developing serious infection, which should be treated appropriately with antibiotics. In those with significant symptoms, chemotherapy, immunotherapy, or chemoimmunotherapy may be used. Depending on the individual's age, physical condition, and whether they have the del(17p) or TP53 mutation, different first line treatments may be offered. As of 2021, BTK inhibitors such as ibrutinib and acalabrutinib are often recommended for first line treatment of CLL. The medications fludarabine, cyclophosphamide, and rituximab were previously the initial treatment in those who are otherwise healthy. CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. In 2021, the estimated incidence of CLL in the United States is 21,250 new cases and 4,320 deaths. The disease most commonly occurs in people over the age of 65, due to the accumulation of genetic mutations that occur over time. Men are diagnosed around twice as often as women (6.8 to 3.5 ratio). It is much less common in people from Asia. Five-year survival following diagnosis is approximately 83% in the United States. It represents less than 1% of deaths from cancer.

Reference
Wiki: Chronic lymphocytic leukemia

    Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes (neutrophils, eosinophils and basophils) and their precursors is found; characteristic increase in basophils is clinically relevant. It is a type of myeloproliferative neoplasm associated with a characteristic chromosomal translocation called the Philadelphia chromosome. CML is largely treated with targeted drugs called tyrosine-kinase inhibitors (TKIs) which have led to dramatically improved long-term survival rates since 2001. These drugs have revolutionized treatment of this disease and allow most patients to have a good quality of life when compared to the former chemotherapy drugs. In Western countries, CML accounts for 15¨C25% of all adult leukemias and 14% of leukemias overall (including the pediatric population, where CML is less common).

Reference
Wiki: Chronic myelogenous leukemia

    Myeloid leukemia is a type of leukemia affecting myeloid tissue. Types include: Acute myeloid leukemia: A cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Chronic myelogenous leukemia: A cancer of the white blood cells. Acute megakaryoblastic leukemia: A life-threatening leukemia in which malignant megakaryoblasts proliferate abnormally and injure various tissues. Blastic plasmacytoid dendritic cell neoplasm: A rare hematologic malignancy which is a malignancy of plasmacytoid dendritic cells.

Reference
Wiki: Chronic myelogenous leukemia/chronic myeloid leukemia

    A myeloid leukemia that is characterized by over production of white blood cells.

Reference
DiseaseOntology: Chronic myeloid leukemia

    Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell. CMML shows characteristics of a myelodysplastic syndrome (MDS); a disorder that produces abnormal looking blood cells, and a myeloproliferative neoplasm (MPN); a disorder characterised by the overproduction of blood cells. For this reason, CMML was reclassified as a MDS/MPN overlap disorder in 2002. For a diagnosis of CMML, the World Health Organization (WHO) states that the blood monocyte count must be >1x109/L, no Philadelphia chromosome or mutations in the PDGFRA or PDGFRB gene should be present, the blast count must be <20% and dysplasia of at least one lineage of myeloid blood cell should be present. Azacitidine is a drug used to treat CMML and is approved by the Food and Drug Administration (FDA) and the European Medicines Agency. Stem cell transplant is also used to treat CMML, and involves the transplantation of donor haematopoietic stem cells into the recipient. Blood transfusion and erythropoietin are used to treat disease associated anaemia.

Reference
Wiki: Chronic myelomonocytic leukemia

    Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described, both having different signs and symptoms, and are caused by mutations in different genes. Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions taking place in the liver. These reactions process excess nitrogen, generated when protein is used for energy by the body, to make urea, which is excreted by the kidneys.

Reference
Wiki: Citrullinemia

    A blood coagulation disease that is characterized by an impaired blood clotting resulting from a lack deficiency of a the fibrinogen protein (coagulation factor I).

Reference
DiseaseOntology: Congenital afibrinogenemia

    Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal quantity of hemoglobin in the blood. CDA may be transmitted by both parents autosomal recessively or dominantly.

Reference
Wiki: Congenital dyserythropoietic anemia

    Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammonia is a substance that contains nitrogen. It is a product of the catabolism of protein. It is converted to the less toxic substance urea prior to excretion in urine by the kidneys. The metabolic pathways that synthesize urea involve reactions that start in the mitochondria and then move into the cytosol. The process is known as the urea cycle, which comprises several enzymes acting in sequence. It is greatly exacerbated by common zinc deficiency, which raises ammonia levels further.

Reference
Wiki: Congenital hyperammonemia

    Venetoclax, sold under the brand names Venclexta and Venclyxto, is a medication used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML). The most common side effects are low levels of neutrophils (a type of white blood cell), diarrhea, nausea, anemia (low red blood cell counts), nose and throat infection and tiredness. Venetoclax attaches to a protein called Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the cells survive for longer in the body and makes them resistant to cancer medicines. By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression of the disease.

Reference
Wiki: CPT-resistant leukemia

    Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It causes a temporary condition with a low absolute neutrophil count and because the neutrophils make up the majority of circulating white blood cells it places the body at severe risk of inflammation and infection. In comparison to severe congenital neutropenia, it responds well to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count, shortens the cycle length, as well decreases the severity and frequency of infections.

Reference
Wiki: Cyclical neutropenia

    A beta thalassemia that is characterized by decreased or absent synthesis of both the delta- and beta-globin chains, which leads to a compensatory increase in fetal gamma-chain synthesis. This disorder results in a microcytic anemia that is clinically mild.

Reference
DiseaseOntology: Delta beta-thalassemia

    A pure red-cell aplasia that is characterized by anemia (low red blood cell counts) with decreased erythroid progenitors in the bone marrow and has_material_basis_insufficient levels of red blood cells due to bone marrow dysfunction.

Reference
DiseaseOntology: Diamond-blackfan anemia

    The dysfibrinogenemias consist of three types of fibrinogen disorders in which a critical blood clotting factor, fibrinogen, circulates at normal levels but is dysfunctional. Congenital dysfibrinogenemia is an inherited disorder in which one of the parental genes produces an abnormal fibrinogen. This fibrinogen interferes with normal blood clotting and/or lysis of blood clots. The condition therefore may cause pathological bleeding and/or thrombosis. Acquired dysfibrinogenemia is a non-hereditary disorder in which fibrinogen is dysfunctional due to the presence of liver disease, autoimmune disease, a plasma cell dyscrasias, or certain cancers. It is associated primarily with pathological bleeding. Hereditary fibrinogen A¦Á-Chain amyloidosis is a sub-category of congenital dysfibrinogenemia in which the dysfunctional fibrinogen does not cause bleeding or thrombosis but rather gradually accumulates in, and disrupts the function of, the kidney. Congenital dysfibrinogenemia is the commonest of these three disorders. Some 100 different genetic mutations occurring in more than 400 families have been found to cause it. All of these mutations as well as those causing hereditary fibrinogen A¦Á-Chain amyloidosis exhibit partial penetrance, i.e. only some family members with one of these mutant genes develop dysfibrinogenemia-related symptoms. While both of these congenital disorders as well as acquired dysfibrinogenemia are considered very rare, it is estimated that ~0.8% of individuals with venous thrombosis have either a congenital or acquired dysfibrinogenemia. Hence, the dysfibrinogenemia disorders may be highly under-diagnosed conditions due to isolated thrombotic events that are not appreciated as reflecting an underlying fibrinogen disorder. Congenital dysfibrinogenemia is distinguished from a similar inherited disorder, congenital hypodysfibrinogenemia. Both disorders involve the circulation of dysfunctional fibrinogen but in congenital hypodysfibrinogenemia plasma fibrinogen levels are low while in congenital dysfibrinogenemia they are normal. Furthermore, the two disorders involve different gene mutations and inheritance patterns as well as somewhat different symptoms.

Reference
Wiki: Dysfibrinogenemia

    A hyperthyroxinemia that is characterized by an increased affinity for thyroxine (T4) by transthyretin in clinically euthyroid individuals and that has_material_basis_in heterozygous mutation in the TTR gene on chromosome 18q12.

Reference
DiseaseOntology: dystransthyretinemic hyperthyroxinemia

    Frydman et al. (1995) described a 7-month-old boy with gross motor delay and failure to thrive who presented with rhabdomyolysis following an acute asthmatic episode. During hospitalization, the ECG changed from normal sinus rhythm to a type I Wolff-Parkinson-White pattern. Duchenne muscular dystrophy (DMD; 310200) was suspected based on elevated creatine kinase serum levels, muscle biopsy, and family history. The diagnosis was confirmed by molecular analyses which documented a deletion in the dystrophin gene (300377) in the propositus, and in an affected male cousin of his mother. 'Idiopathic' hyperCKemia was found in the propositus, his father, and 5 of his relatives. Frydman et al. (1995) suggested that the unusually early and severe manifestations of DMD in this patient may be related to the coincidental inheritance of a maternal DMD gene and of a paternal gene causing hyperCKemia.

Reference
OMIM: Elevated serum creatine phosphokinase

    Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the person's red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctive erythrocytes are sometimes referred to as elliptocytes or ovalocytes. It is one of many red-cell membrane defects. In its severe forms, this disorder predisposes to haemolytic anaemia. Although pathological in humans, elliptocytosis is normal in camelids.

Reference
Wiki: Elliptocytosis

    Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by covalent bonds, and are found in the bacterial capsule, the outermost membrane of cell envelope of Gram-negative bacteria, such as E. coli and Salmonella. Today, the term endotoxin is often used synonymously with LPS, although there are a few endotoxins (in the original sense of toxins that are inside the bacterial cell that are released when the cell disintegrates) that are not related to LPS, such as the so-called delta endotoxin proteins produced by Bacillus thuringiensis. Lipopolysaccharides can have substantial impacts on human health, primarily through interactions with the immune system. LPS is a potent activator of the immune system and pyrogen (agent that causes fever). In severe cases, LPS can play a role in causing septic shock. In lower levels and over a longer time period, there is evidence LPS may play an important and harmful role in autoimmunity, obesity, depression, and cellular senescence.

Reference
Wiki: Endotoxemia

    Polycythemia (also known as polycythaemia) is a laboratory finding in which the hematocrit (the volume percentage of red blood cells in the blood) and/or hemoglobin concentration are increased in the blood. Polycythemia is sometimes called erythrocytosis, and there is significant overlap in the two findings, but the terms are not the same: polycythemia describes any increase in hematocrit and/or hemoglobin, while erythrocytosis describes an increase specifically in the number of red blood cells in the blood. Polycythemia has many causes. It can describe an increase in the number of red blood cells ("absolute polycythemia") or to a decrease in the volume of plasma ("relative polycythemia"). Absolute polycythemia can be due to genetic mutations in the bone marrow ("primary polycythemia"), physiologic adaptations to one's environment, medications, and/or other health conditions. Laboratory studies such as serum erythropoeitin levels and genetic testing might be helpful to clarify the cause of polycythemia if the physical exam and patient history do not reveal a likely cause. Mild polycythemia on its own is often asymptomatic. Treatment for polycythemia varies, and typically involves treating its underlying cause. Treatment of primary polycythemia (see polycythemia vera) could involve phlebotomy, antiplatelet therapy to reduce risk of blood clots, and additional cytoreductive therapy to reduce the number of red blood cells produced in the bone marrow.

Reference
Wiki: Erythrocytosis

    Acute erythrocyte leukemia is a rare form of acute myeloid leukemia (less than 5% of AML cases) where the myeloproliferation is of erythrocytic precursors. It is defined as type "M6" under the FAB classification.

Reference
Wiki: Erythroleukemia

    Polycythemia (also known as polycythaemia) is a laboratory finding in which the hematocrit (the volume percentage of red blood cells in the blood) and/or hemoglobin concentration are increased in the blood. Polycythemia is sometimes called erythrocytosis, and there is significant overlap in the two findings, but the terms are not the same: polycythemia describes any increase in hematocrit and/or hemoglobin, while erythrocytosis describes an increase specifically in the number of red blood cells in the blood.

Reference
Wiki: familial erythrocytosis

    In hematology, hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes. There are inherited and non-inherited (acquired) causes of HLH.

Reference
Wiki: Familial hemophagocytic lymphohistiocytosis

    Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL cholesterol), in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly (abnormal trafficking). Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH (such as dietary modification and statin tablets). Nevertheless, treatment (including higher statin doses) is usually effective. FH is classified as a type 2 familial dyslipidemia. There are five types of familial dyslipidemia (not including subtypes), and each are classified from both the altered lipid profile and by the genetic abnormality. For example, high LDL (often due to LDL receptor defect) is type 2. Others include defects in chylomicron metabolism, triglyceride metabolism, and metabolism of other cholesterol-containing particles, such as VLDL and IDL. About 1 in 100 to 200 people have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare but important to know, including gain-of-function mutations in PCSK9, the molecular "scissor" of LDL receptors, resulting in less LDLR available. PCSK9 mutations cause less than 5% of cases of FH according to most epidemiologic studies. People who have one abnormal copy (are heterozygous) of the LDLR gene may develop cardiovascular disease prematurely at the age of 30 to 40. Having two abnormal copies (being homozygous) may cause severe cardiovascular disease in childhood. Heterozygous FH is a common genetic disorder, inherited in an autosomal dominant pattern, occurring in 1:250 people in most countries; homozygous FH is much rarer, occurring in 1 in 300,000 people. Heterozygous FH is normally treated with statins, bile acid sequestrants, or other lipid-lowering agents that lower cholesterol levels. New cases are generally offered genetic counseling. Homozygous FH often does not respond to medical therapy and may require other treatments, including LDL apheresis (removal of LDL in a method similar to dialysis) and occasionally liver transplantation.

Reference
Wiki: Familial hypercholesterolemia

    Familial hyperinsulinism, also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur (Thornton et al., 1998).

Reference
OMIM: familial hyperinsulinemic hypoglycemia

    Tangier disease or hypoalphalipoproteinemia is an extremely rare inherited disorder characterized by a severe reduction in the amount of high density lipoprotein (HDL), often referred to as "good cholesterol", in the bloodstream. Worldwide, approximately 100 cases have even been identified. The disorder was originally discovered on Tangier Island off the coast of Virginia, but has now been identified in people from many countries.

Reference
Wiki: Familial hypoalphalipoproteinemia

    Abetalipoproteinemia (also known as: Bassen¨CKornzweig syndrome, microsomal triglyceride transfer protein deficiency disease, MTP deficiency, and betalipoprotein deficiency syndrome[2]) is a disorder characterized by abnormal absorption of fat and fat-soluble vitamins from food.[3] It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.

Reference
Wiki: familial hypobetalipoproteinemia

    Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL; although uncommon. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day.

Reference
Wiki: Familial hypocalciuric hypercalcemia

    A blood platelet disease characterized by autosomal dominant inheritance of delayed onset bleeding after challenge, moderate to severe bleeding tendencies, frequent ecchymoses, mucocutaneous bleeding, muscle and joint bleeds and platelet alpha-granule degredation that has_material_basis_in heterozygous tandem duplication of the PLAU gene on chromosome 10q22.

Reference
DiseaseOntology: Familial platelet disorder

    Fanconi anemia (FA) is a rare, autosomal recessive, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia (the inability to produce blood cells) by age 40. About 60¨C75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure. FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination. The well-known cancer susceptibility genes BRCA1 and BRCA2 are also examples of FA genes (FANCS and FANCD1 respectively), and biallelic mutation of any of the two genes usually results in an embryonically lethal outcome, and should the proband come to term, experience a severe form of Fanconi anemia. Treatment with androgens and hematopoietic (blood cell) growth factors can help bone marrow failure temporarily, but the long-term treatment is bone marrow transplant if a donor is available. Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA crosslinking, such as mitomycin C. The typical age of death was 30 years in 2000. FA occurs in about one per 130,000 live births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa. The disease is named after the Swiss pediatrician who originally described this disorder, Guido Fanconi. Some forms of Fanconi anemia, such as those of complementation group D1, N, and S, are embryonically lethal in most cases, which might account for the rare observation of these complementation groups. It should not be confused with Fanconi syndrome, a kidney disorder also named after Fanconi.

Reference
Wiki: Fanconi anemia

    Fanconi syndrome or Fanconi's syndrome (English: /f¨»?n?ko?ni/, /f?n-/) is a syndrome of inadequate reabsorption in the proximal renal tubules[1] of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from toxic heavy metals), or by adverse drug reactions.[2] It results in various small molecules of metabolism being passed into the urine instead of being reabsorbed from the tubular fluid (for example, glucose, amino acids, uric acid, phosphate, and bicarbonate). Fanconi syndrome affects the proximal tubules, namely, the proximal convoluted tubule (PCT), which is the first part of the tubule to process fluid after it is filtered through the glomerulus, and the proximal straight tubule (pars recta), which leads to the descending limb of loop of Henle.

Reference
Wiki: Fanconi renotubular syndrome

    Glanzmann's thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.

Reference
Wiki: Glanzmann thrombasthenia

    An organic acidemia characterized by impaired lysine, hydroxylysine, and tryptophan metabolism, increased urinary excretion of glutaric acid, and accumulation of 3-hydroxyglutaric and glutaric acid, resulting in striatal injury and a severe dystonic dyskinetic movement disorder that has_material_basis_in homozygous or compound heterozygous mutation in the GCDH gene on chromosome 19p13.

Reference
DiseaseOntology: Glutaric acidemia I

    A blood platelet disease characterized by selective deficiency in the number and contents of platelet alpha-granules, macrothrombocytopenia, enlarged platelets, myelofibrosis, splenomegaly, and increased bleeding time that has_material_basis_in homozygous or compound heterozygous mutation in the NBEAL2 gene on chromosome 3p21.

Reference
DiseaseOntology: Gray platelet syndrome

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Aarbizon

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Andrew-Minneapolis

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Attleboro

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Beijing

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin brem-sur-mer

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Colima

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Creteil

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin D

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Douala

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Ernz

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Gambara

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Harbin

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Hazebrouck

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Helsinki

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Hinwil

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin I

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin J

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Kofu

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin La Coruna

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Las Palmas

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Lodz

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Luxembourg

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Malaysia

    The phytoglobin-nitric oxide cycle is a metabolic pathway induced in plants under hypoxic conditions which involves nitric oxide (NO) and phytoglobin (Pgb). It provides an alternative type of respiration to mitochondrial electron transport under the conditions of limited oxygen supply. Phytoglobin in hypoxic plants acts as part of a soluble terminal nitric oxide dioxygenase system, yielding nitrate ion from the reaction of oxygenated phytoglobin with NO. Class 1 phytoglobins are induced in plants under hypoxia, bind oxygen very tightly at nanomolar concentrations, and can effectively scavenge NO at oxygen levels far below the saturation of cytochrome c oxidase. In the course of the reaction, phytoglobin is oxidized to metphytoglobin which has to be reduced for continuous operation of the cycle. Nitrate is reduced to nitrite by nitrate reductase, while NO is mainly formed due to anaerobic reduction of nitrite which may take place in mitochondria by complex III and complex IV in the absence of oxygen, in the side reaction of nitrate reductase, or by electron transport proteins on the plasma membrane. The overall reaction sequence of the cycle consumes NADH and can contribute to the maintenance of ATP level in highly hypoxic conditions.

Reference
DiseaseOntology: Hemoglobin Mito

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Miyano

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Nevers

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Nigeria

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Passy

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Philly

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Porto Alegre

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Questembert

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Rahere

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Rainier

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Ramona

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Rouen

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Saale

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Savaria

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Tsurumai

    A Cornelia de Lange syndrome that has_material_basis_in heterozygous mutation in the SMC3 gene on chromosome 10q25.2.

Reference
DiseaseOntology: Hemoglobin Val de Marne

    Hemoglobinopathy is the medical term for a group of inherited blood disorders involving the hemoglobin, the protein of red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits. There are two main groups: abnormal structural hemoglobin variants caused by mutations in the hemoglobin genes, and the thalassemias, which are caused by an underproduction of otherwise normal hemoglobin molecules. The main structural hemoglobin variants are HbS, HbE and HbC. The main types of thalassemia are alpha-thalassemia and beta thalassemia. The two conditions may overlap because some conditions which cause abnormalities in hemoglobin proteins also affect their production. Some hemoglobin variants do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies.

Reference
Wiki: Hemoglobin Valletta

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Villaverde

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Villejuif

    An alpha thalassemia that has_material_basis_in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

Reference
DiseaseOntology: Hemoglobin Wien

    Hemoglobinopathy is the medical term for a group of inherited blood disorders involving the hemoglobin, the protein of red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits. There are two main groups: abnormal structural hemoglobin variants caused by mutations in the hemoglobin genes, and the thalassemias, which are caused by an underproduction of otherwise normal hemoglobin molecules. The main structural hemoglobin variants are HbS, HbE and HbC. The main types of thalassemia are alpha-thalassemia and beta thalassemia. The two conditions may overlap because some conditions which cause abnormalities in hemoglobin proteins also affect their production. Some hemoglobin variants do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies.

Reference
Wiki: Hemoglobinopathy

    A normocytic anemia that is characterized by the rate of descruction of red blood cells exceeding the rate than they can be made.

Reference
DiseaseOntology: Hemolytic anemia

    Haemophilia, or hemophilia[6] (from Ancient Greek ¦Á?¦Ì¦Á (ha?ma) 'blood', and ¦Õ¦É¦Ë?¦Á (phil¨ªa) 'love of'),[7] is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding.[2][3] This results in people bleeding for a longer time after an injury, easy bruising, and an increased risk of bleeding inside joints or the brain.[1] Those with a mild case of the disease may have symptoms only after an accident or during surgery.[1] Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or a altered level of consciousness.[1]

Reference
Wiki: Hemophilia

    A hereditary cancer syndrome (familial/family cancer syndrome, inherited cancer syndrome, cancer predisposition syndrome, cancer syndrome, etc.) is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancer and may also cause early onset of these cancers. Hereditary cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors. Many of these syndromes are caused by mutations in tumor suppressor genes, genes that are involved in protecting the cell from turning cancerous. Other genes that may be affected are DNA repair genes, oncogenes and genes involved in the production of blood vessels (angiogenesis). Common examples of inherited cancer syndromes are hereditary breast-ovarian cancer syndrome and hereditary non-polyposis colon cancer (Lynch syndrome).

Reference
Wiki: Hereditary cancer-predisposing syndrome

    Homocystinuria and megaloblastic anemia is an autosomal recessive inborn error of metabolism resulting from defects in the cobalamin (vitamin B12)-dependent pathway that converts homocysteine to methionine, which is catalyzed by methionine synthase (MTR; 156570). Clinical features are somewhat variable, but include delayed psychomotor development, hypotonia, megaloblastic anemia, homocystinuria, and hypomethioninemia, all of which respond to cobalamin supplementation. Methylmalonic aciduria is not present. Two complementation groups have been described based on fibroblast studies: CblE and CblG (250940) (Watkins and Rosenblatt, 1988). Cells from patients with CblE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent. Cells from patients with CblG have defects in the methionine synthase enzyme under both conditions (summary by Leclerc et al., 1996).

Reference
OMIM: Homocystinuria-megaloblastic anemia

    Bilirubin (BR) (from the Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the destruction of aged or abnormal red blood cells. In the first step of bilirubin synthesis, the heme molecule is stripped from the hemoglobin molecule. Heme then passes through various processes of porphyrin catabolism, which varies according to the region of the body in which the breakdown occurs. For example, the molecules excreted in the urine differ from those in the feces. The production of biliverdin from heme is the first major step in the catabolic pathway, after which the enzyme biliverdin reductase performs the second step, producing bilirubin from biliverdin. Ultimately, bilirubin is broken down within the body, and its metabolites excreted through bile and urine; elevated levels may indicate certain diseases. It is responsible for the yellow color of healing bruises and the yellow discoloration in jaundice. The bacterial enzyme bilirubin reductase is responsible for the breakdown of bilirubin in the gut. One breakdown product, urobilin, is the main component of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown color of feces. Although bilirubin is usually found in animals rather than plants, at least one plant species, Strelitzia nicolai, is known to contain the pigment.

Reference
Wiki: Hyperbilirubinemia

    The enterohepatic circulation of bile salts is an important physiological route to recycle bile salts and ensure intestinal absorption of dietary lipids. The Na(+)-taurocholate cotransporting polypeptide SLC10A1 (NTCP) plays a key role in this process as the major transporter of conjugated bile salts from the plasma compartment into the hepatocyte.

Reference
Pubmed: Hypercholanemia

    An amino acid metabolic disorder that involves an abnormally large level of homocysteine in the blood.

Reference
DiseaseOntology: Hyperhomocysteinemia

    Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood.[2] The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding.[3] Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.[3]

Reference
Wiki: Hyperlipoproteinemia

    Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia. Phenylalanine concentrations are routinely screened in newborns by the neonatal heel prick (Guthrie test), which takes a few drops of blood from the heel of the infant. Standard phenylalanine concentrations in unaffected persons are about 2-6mg/dl (120¨C360 ¦Ìmol/L) phenylalanine concentrations in those with untreated hyperphenylalaninemia can be up to 20 mg/dL (1200 ¦Ìmol/L). Measurable IQ deficits are often detected as phenylalanine levels approach 10 mg/dL (600 mol/L). Phenylketonuria (PKU)-like symptoms, including more pronounced developmental defects, skin irritation, and vomiting, may appear when phenylalanine levels are near 20 mg/dL (1200 mol/L).Hyperphenylalaninemia is a recessive hereditary metabolic disorder that is caused by the body's failure to convert phenylalanine to tyrosine as a result of the entire or partial absence of the enzyme phenylalanine hydroxylase.

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Wiki: Hyperphenylalaninemia

    Hyperthyroxinemia is a thyroid disease where the serum levels of thyroxine are higher than expected. Thyroxine or tetraiodothyronine (T4) is produced by the thyroid gland. The term is sometimes used to refer to hyperthyroidism, but hyperthyroidism is a more general term. When the level of thyroxine (T4) in the blood exceeds normal range, it can lead to symptoms such as irritability and unexplained weight loss. Types include: Familial dysalbuminemic hyperthyroxinemia Familial euthyroid hyperthyroxinemia Thyroid hormone resistance syndrome

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Wiki: Hyperthyroxinemia

    Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and high triglyceride levels are associated with atherosclerosis, even in the absence of hypercholesterolemia (high cholesterol levels) and predispose to cardiovascular disease.

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Wiki: Hypertriglyceridemia

    Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL; although uncommon. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day.

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Wiki: Hypocalciuric hypercalcemia

    An inherited metabolic disorder characterized by neonatal macrosomia, asymmetrical overgrowth, and recurrent, severe hypoinsulinemic hypoglycemia in infancy that has_material_basis_in heterozygous activating mutation in the AKT2 gene on chromosome 19q13.2.

Reference
DiseaseOntology: Hypoinsulinemic hypoglycemia with hemihypertrophy

    Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura characterized by a low platelet count in the absence of other causes, and accompanied by a red-purple rash called purpura. It leads to an increased risk of bleeding. ITP manifests in two distinct clinical syndromes: an acute form observed in children, and chronic conditions observed in adults. The acute form often follows an infection and typically resolves within two months, while chronic immune thrombocytopenia persists for longer than six months and its specific cause is unknown. ITP is considered an autoimmune disease, as antibodies against several platelet surface structures (antigens) can be detected. Diagnosis of ITP involves identifying a low platelet count through a complete blood count, a common blood test. However, since the diagnosis relies on excluding other potential causes of a low platelet count, additional investigations, such as a bone marrow biopsy, may be necessary in certain cases. For mild cases, careful observation may be sufficient. However, in instances of very low platelet counts or significant bleeding, treatment options may include corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, or immunosuppressive medications. Refractory ITP, which does not respond to conventional treatment or shows constant relapse after splenectomy, requires treatment to reduce the risk of significant bleeding. Platelet transfusions may be used in severe cases with extremely low platelet counts in individuals experiencing bleeding. In some cases, the body may compensate by producing abnormally large platelets.

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Wiki: Immune thrombocytopenia

    Finberg et al. (2008) referred to this phenotype as iron-refractory iron deficiency anemia (IRIDA) and reviewed the key features: a congenital hypochromic, microcytic anemia; a very low mean corpuscular erythrocyte volume; a low transferrin saturation; abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron; and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. The authors noted that although urinary levels of hepcidin (606464) are typically undetectable in individuals with iron deficiency, in 5 individuals with IRIDA urinary hepcidin/creatinine ratios were within or above the normal range.

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OMIM: Iron-refractory iron deficiency anemia

    Juvenile myelomonocytic leukemia (JMML) is a rare form of chronic leukemia (cancer of the blood) that affects children, commonly those aged four and younger. The name JMML now encompasses all diagnoses formerly referred to as juvenile chronic myeloid leukemia (JCML), chronic myelomonocytic leukemia of infancy, and infantile monosomy 7 syndrome. The average age of patients at diagnosis is two (2) years old. The World Health Organization has included JMML as a subcategory of myelodysplastic and myeloproliferative disorders.

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Wiki: Juvenile myelomonocytic leukemia

    Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood. It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells). In a study based in the US, the average age of diagnosis was 66.5 years whereas in a French study the median age at diagnosis was 59 years (with an age range of 12¨C87 years old). In the French study, only 26% of patients were younger than 50 years which suggests that this disorder is associated with older age at diagnosis. Due to lack of presenting symptoms, the disorder is likely to be underdiagnosed in the general population.

Reference
Wiki: Large granular lymphocytic leukemia

    Leukemia (also spelled leukaemia and pronounced loo-KEE-mee-?) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy. The exact cause of leukemia is unknown. A combination of genetic factors and environmental (non-inherited) factors are believed to play a role. Risk factors include smoking, ionizing radiation, petrochemicals (such as benzene), prior chemotherapy, and Down syndrome. People with a family history of leukemia are also at higher risk. There are four main types of leukemia¡ªacute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)¡ªas well as a number of less common types. Leukemias and lymphomas both belong to a broader group of tumors that affect the blood, bone marrow, and lymphoid system, known as tumors of the hematopoietic and lymphoid tissues. Treatment may involve some combination of chemotherapy, radiation therapy, targeted therapy, and bone marrow transplant, in addition to supportive care and palliative care as needed. Certain types of leukemia may be managed with watchful waiting. The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world. Five-year survival rate is 65% in the United States. In children under 15 in first-world countries, the five-year survival rate is greater than 60% or even 90%, depending on the type of leukemia. In children with acute leukemia who are cancer-free after five years, the cancer is unlikely to return. In 2015, leukemia was present in 2.3 million people worldwide and caused 353,500 deaths. In 2012, it had newly developed in 352,000 people. It is the most common type of cancer in children, with three-quarters of leukemia cases in children being the acute lymphoblastic type. However, over 90% of all leukemias are diagnosed in adults, with CLL and AML being most common in adults. It occurs more commonly in the developed world.

Reference
Wiki: Leukemia

    Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a Glanzmann thrombasthenia-like bleeding tendency.

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Wiki: Leukocyte adhesion deficiency

    Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years. Risk factors include having a family history of the disease, with 10% of those who develop CLL having such ancestry. Exposure to Agent Orange, certain insecticides, sun exposure, exposure to hepatitis C virus, and common infections are also considered risk factors. CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. CLL is divided into two main types: Those with a mutated IGHV gene Those without. Diagnosis is typically based on blood tests finding high numbers of mature lymphocytes and smudge cells. Early-stage CLL in asymptomatic cases responds better to careful observation, as there is no evidence that early intervention treatment can alter the course of the disease. Immune defects occur early in the course of CLL and these increase the risk of developing serious infection, which should be treated appropriately with antibiotics. In those with significant symptoms, chemotherapy, immunotherapy, or chemoimmunotherapy may be used. Depending on the individual's age, physical condition, and whether they have the del(17p) or TP53 mutation, different first line treatments may be offered. As of 2021, BTK inhibitors such as ibrutinib and acalabrutinib are often recommended for first line treatment of CLL. The medications fludarabine, cyclophosphamide, and rituximab were previously the initial treatment in those who are otherwise healthy. CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. In 2021, the estimated incidence of CLL in the United States is 21,250 new cases and 4,320 deaths. The disease most commonly occurs in people over the age of 65, due to the accumulation of genetic mutations that occur over time. Men are diagnosed around twice as often as women (6.8 to 3.5 ratio). It is much less common in people from Asia. Five-year survival following diagnosis is approximately 83% in the United States. It represents less than 1% of deaths from cancer.

Reference
Wiki: Lymphocytic leukemia

    Giant platelet disorders, also known as macrothrombocytopenia, are rare disorders featuring abnormally large platelets, thrombocytopenia and a tendency to bleeding. Giant platelets cannot stick adequately to injured blood vessel walls, resulting in abnormal bleeding when injured. Giant platelet disorder occurs for inherited diseases like Bernard¨CSoulier syndrome, gray platelet syndrome and May¨CHegglin anomaly.

Reference
Wiki: Macrothrombocytopenia

    Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood.[1] If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.

Reference
Wiki: Mast cell leukemia

    Mastocytosis, a type of mast cell disease, is a rare disorder affecting both children and adults caused by the accumulation of functionally defective mast cells (also called mastocytes) and CD34+ mast cell precursors.[1]

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Wiki: Mastocytosis

    Methemoglobinemia is a clinical condition in which more than 1% of hemoglobin is oxidized to methemoglobin, a type of hemoglobin that contains the ferric (Fe3+) form of iron. Patients with hemoglobin M are cyanotic but otherwise asymptomatic. If the mutation occurs in the hemoglobin alpha subunit (141800), cyanosis is apparent at birth, whereas if the beta chain is affected, cyanosis appears later or intensifies when beta subunit production increases. If a newborn carries a fetal M hemoglobin (gamma subunit; 142250), cyanosis disappears when the complete gamma-beta-switch occurs (summary by Mansouri and Lurie, 1993).

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OMIM: Methemoglobinemia

    A disorder of sexual development characterized by severely reduced 17,20-lyase activity of CYP17A1, sex steroid deficiency with no deficiency in glucocorticoid and mineralocorticoid reserves, absent or disturbed pubertal development, and mild to severe methemoglobinemia that has_material_basis_in homozygous or compound heterozygous mutation in the CYB5A gene on chromosome 18q22.3.

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DiseaseOntology: Methemoglobinemia and ambiguous genitalia

    Methylmalonic acidemias, also called methylmalonic acidurias, are a group of inherited metabolic disorders, that prevent the body from properly breaking down proteins and fats. This leads to a buildup of a toxic level of methylmalonic acid in body liquids and tissues. Due to the disturbed branched-chain amino acids (BCAA) metabolism, they are among the classical organic acidemias. Methylmalonic acidemias have varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder. The first symptoms may begin as early as the first day of life or as late as adulthood. Symptoms can range from mild to life-threatening. Some forms can result in death if undiagnosed or left untreated. Methylmalonic acidemias are found with an equal frequency across ethnic boundaries.

Reference
Wiki: Methylmalonic acidemia

    A methylmalonic acidemia that has_material_basis_in deficiency in synthesis of both AdoCbl and MeCbl (cblC) and is characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective enzymes methylmalonyl-CoA mutase.

Reference
DiseaseOntology: methylmalonic aciduria and homocystinuria type cblC

    Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein is usually found during standard laboratory blood or urine tests. MGUS resembles multiple myeloma and similar diseases, but the levels of antibodies are lower, the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, and it rarely has symptoms or major problems. However, since MGUS can lead to multiple myeloma, which develops at the rate of about 1.5% a year, or other symptomatic conditions, yearly monitoring is recommended. The progression from MGUS to multiple myeloma usually involves several steps. In rare cases, it may also be related with a slowly progressive symmetric distal sensorimotor neuropathy.

Reference
Wiki: Monoclonal gammopathy of uncertain significance

    A myeloid neoplasm that is located_in the plasma cells in bone marrow.

Reference
DiseaseOntology: Multiple myeloma

    A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia. Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead. Problems with blood cell formation result in some combination of low red blood cell, platelet, and white blood cell counts. Some types of MDS cause an increase in the production of immature blood cells (called blasts), in the bone marrow or blood. The different types of MDS are identified based on the specific characteristics of the changes in the blood cells and bone marrow. Treatments may include supportive care, drug therapy, and hematopoietic stem cell transplantation. Supportive care may include blood transfusions, medications to increase the making of red blood cells, and antibiotics. Drug therapy may include the medications lenalidomide, antithymocyte globulin, and azacitidine. Some people can be cured by chemotherapy followed by a stem-cell transplant from a donor. About seven per 100,000 people are affected by MDS; about four per 100,000 people newly acquire the condition each year. The typical age of onset is 70 years. The prognosis depends on the type of cells affected, the number of blasts in the bone marrow or blood, and the changes present in the chromosomes of the affected cells. The average survival time following diagnosis is 2.5 years. MDS was first recognized in the early 1900s; it came to be called myelodysplastic syndrome in 1976.

Reference
Wiki: Myelodysplasia

    A bone marrow cancer that is characterized by under production of white blood cells, red blood cells and platelets.

Reference
DiseaseOntology: Myelodysplastic syndrome

    Myeloid tissue, in the bone marrow sense of the word myeloid (myelo- + -oid), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (myelo- + -genous) is any tissue of, or arising from, bone marrow; in these senses the terms are usually used synonymously, as for example with chronic myeloid/myelogenous leukemia. In hematopoiesis, myeloid cells, or myelogenous cells are blood cells that arise from a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets (the common myeloid progenitor, that is, CMP or CFU-GEMM), or in a narrower sense also often used, specifically from the lineage of the myeloblast (the myelocytes, monocytes, and their daughter types). Thus, although all blood cells, even lymphocytes, are normally born in the bone marrow in adults, myeloid cells in the narrowest sense of the term can be distinguished from lymphoid cells, that is, lymphocytes, which come from common lymphoid progenitor cells that give rise to B cells and T cells. Those cells' differentiation (that is, lymphopoiesis) is not complete until they migrate to lymphatic organs such as the spleen and thymus for programming by antigen challenge. Thus, among leukocytes, the term myeloid is associated with the innate immune system, in contrast to lymphoid, which is associated with the adaptive immune system. Similarly, myelogenous usually refers to nonlymphocytic white blood cells, and erythroid can often be used to distinguish "erythrocyte-related" from that sense of myeloid and from lymphoid. The word myelopoiesis has several senses in a way that parallels those of myeloid, and myelopoiesis in the narrower sense is the regulated formation specifically of myeloid leukocytes (myelocytes), allowing that sense of myelopoiesis to be contradistinguished from erythropoiesis and lymphopoiesis (even though all blood cells are normally produced in the marrow in adults). Myeloid neoplasms always concern bone marrow cell lineage and are related to hematopoietic cells. Myeloid tissue can also be present in the liver and spleen in fetuses, and sometimes even in adults as well, which leads to extramedullary hematopoiesis. There is one other sense of myeloid that means "pertaining to the spinal cord", but it is much less commonly used. Myeloid should not be confused with myelin, referring to an insulating layer covering the axons of many neurons.

Reference
Wiki: Myeloid

    A leukemia that is located_in myeloid tissue.

Reference
DiseaseOntology: Myeloid leukemia

    Myeloid tissue, in the bone marrow sense of the word myeloid (myelo- + -oid), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (myelo- + -genous) is any tissue of, or arising from, bone marrow; in these senses the terms are usually used synonymously, as for example with chronic myeloid/myelogenous leukemia. In hematopoiesis, myeloid cells, or myelogenous cells are blood cells that arise from a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets (the common myeloid progenitor, that is, CMP or CFU-GEMM), or in a narrower sense also often used, specifically from the lineage of the myeloblast (the myelocytes, monocytes, and their daughter types). Thus, although all blood cells, even lymphocytes, are normally born in the bone marrow in adults, myeloid cells in the narrowest sense of the term can be distinguished from lymphoid cells, that is, lymphocytes, which come from common lymphoid progenitor cells that give rise to B cells and T cells. Those cells' differentiation (that is, lymphopoiesis) is not complete until they migrate to lymphatic organs such as the spleen and thymus for programming by antigen challenge. Thus, among leukocytes, the term myeloid is associated with the innate immune system, in contrast to lymphoid, which is associated with the adaptive immune system. Similarly, myelogenous usually refers to nonlymphocytic white blood cells, and erythroid can often be used to distinguish "erythrocyte-related" from that sense of myeloid and from lymphoid. The word myelopoiesis has several senses in a way that parallels those of myeloid, and myelopoiesis in the narrower sense is the regulated formation specifically of myeloid leukocytes (myelocytes), allowing that sense of myelopoiesis to be contradistinguished from erythropoiesis and lymphopoiesis (even though all blood cells are normally produced in the marrow in adults). Myeloid neoplasms always concern bone marrow cell lineage and are related to hematopoietic cells. Myeloid tissue can also be present in the liver and spleen in fetuses, and sometimes even in adults as well, which leads to extramedullary hematopoiesis. There is one other sense of myeloid that means "pertaining to the spinal cord", but it is much less commonly used. Myeloid should not be confused with myelin, referring to an insulating layer covering the axons of many neurons.

Reference
Wiki: Myeloma

    Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled. The overproduction of blood cells is often associated with a somatic mutation, for example in the JAK2, CALR, TET2, and MPL gene markers. In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia.

Reference
Wiki: Myeloproliferative disorder

    Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled. The overproduction of blood cells is often associated with a somatic mutation, for example in the JAK2, CALR, TET2, and MPL gene markers. In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia.

Reference
Wiki: Myeloproliferative neoplasms

    Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li¨CFraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically Acute lymphoblastic leukemia based on blood tests and bone marrow examination. Acute lymphoblastic leukemia is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy typically over a number of years. Treatment usually also includes intrathecal chemotherapy since systemic chemotherapy can have limited penetration into the central nervous system and the central nervous system is a common site for relapse of acute lymphoblastic leukemia. Treatment can also include radiation therapy if spread to the brain has occurred. Stem cell transplantation may be used if the disease recurs following standard treatment. Additional treatments such as Chimeric antigen receptor T cell immunotherapy are being used and further studied. Acute lymphoblastic leukemia affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. Acute lymphoblastic leukemia is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%).

Reference
Wiki: Pediatric acute lymphoblastic leukemia

    A hematopoietic system disease characterized by white blood cells with unusually shaped nuclei that has_material_basis_in heterozygous mutation in LBR on chromosome 1q42.12.

Reference
DiseaseOntology: Pelger-Huet anomaly

    The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle. The presence of this translocation is required for diagnosis of CML; in other words, all cases of CML are positive for BCR-ABL1. (Some cases are confounded by either a cryptic translocation that is invisible on G-banded chromosome preparations, or a variant translocation involving another chromosome or chromosomes as well as the long arm of chromosomes 9 and 22. Other similar but truly Ph-negative conditions are considered CML-like myeloproliferative neoplasms.) However, the presence of the Philadelphia (Ph) chromosome is not sufficiently specific to diagnose CML, since it is also found in acute lymphoblastic leukemia (aka ALL, 25¨C30% of adult cases and 2¨C10% of pediatric cases) and occasionally in acute myelogenous leukemia (AML) as well as mixed-phenotype acute leukemia (MPAL).

Reference
Wiki: Philadelphia-positive leukemia

    A blood platelet disease characterized by autosomal dominant inheritance of increased bleeding tendency, thrombocytopenia, decreased platelet dense granules and ATP secretion, and impaired megakaryocyte maturation that has_material_basis_in heterozygous mutation in the SLFN14 gene on chromosome 17q12.

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DiseaseOntology: Platelet-type bleeding disorder

    P1PK (formerly: P) is a human blood group system (International Society of Blood Transfusion system 003) based upon the A4GALT gene on chromosome 22. The P antigen (later renamed P1) was first described by Karl Landsteiner and Philip Levine in 1927. The P1PK blood group system consists of three glycosphingolipid antigens: Pk, P1 and NOR. In addition to glycosphingolipids, terminal Gal¦Á1¡ú4Gal¦Â structures are present on complex-type N-glycans. The GLOB antigen (formerly P) is now the member of the separate GLOB (globoside) blood group system.

Reference
Wiki: Polyagglutinable erythrocyte syndrome

    A polycythemia that has_material_basis_in factors intrinsic to red cell precursors.

Reference
DiseaseOntology: Primary familial and congenital polycythemia

    Leukemia (also spelled leukaemia and pronounced loo-KEE-mee-?) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy. The exact cause of leukemia is unknown. A combination of genetic factors and environmental (non-inherited) factors are believed to play a role. Risk factors include smoking, ionizing radiation, petrochemicals (such as benzene), prior chemotherapy, and Down syndrome. People with a family history of leukemia are also at higher risk. There are four main types of leukemia¡ªacute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)¡ªas well as a number of less common types. Leukemias and lymphomas both belong to a broader group of tumors that affect the blood, bone marrow, and lymphoid system, known as tumors of the hematopoietic and lymphoid tissues. Treatment may involve some combination of chemotherapy, radiation therapy, targeted therapy, and bone marrow transplant, in addition to supportive care and palliative care as needed. Certain types of leukemia may be managed with watchful waiting. The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world. Five-year survival rate is 65% in the United States. In children under 15 in first-world countries, the five-year survival rate is greater than 60% or even 90%, depending on the type of leukemia. In children with acute leukemia who are cancer-free after five years, the cancer is unlikely to return. In 2015, leukemia was present in 2.3 million people worldwide and caused 353,500 deaths. In 2012, it had newly developed in 352,000 people. It is the most common type of cancer in children, with three-quarters of leukemia cases in children being the acute lymphoblastic type. However, over 90% of all leukemias are diagnosed in adults, with CLL and AML being most common in adults. It occurs more commonly in the developed world.

Reference
Wiki: Primary human acute leukemia

    Propionic acidemia, also known as propionic aciduria or propionyl-CoA carboxylase deficiency (PCC deficiency), is a rare autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia. The disorder presents in the early neonatal period with poor feeding, vomiting, lethargy, and lack of muscle tone. Without treatment, death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or brain damage.

Reference
Wiki: Propionic acidemia

    A congenital nonspherocytic hemolytic anemia that has_material_basis_in homozygous or compound heterozygous mutation in the PKLR gene on chromosome 1q22.

Reference
DiseaseOntology: Pyruvate kinase deficiency of red cells

    Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in children and adults, but not recommended in elderly patients), rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein¨CBarr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion (injected slowly through an IV line). Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza (F.K.A. Tuxella), Rixathon, Ruxience, and Truxima. Common side effects which often occur within two hours of the medication being given include rash, itchiness, low blood pressure, and shortness of breath. Infections are also common. Severe side effects include reactivation of hepatitis B in those previously infected, progressive multifocal leukoencephalopathy, toxic epidermal necrolysis, and death. It is unclear if use during pregnancy is safe for the developing fetus or newborn baby, but it is not proven harmful. Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. When it binds to this protein it triggers cell death. Rituximab was approved for medical use in 1997. It is on the World Health Organization's List of Essential Medicines. Rituximab is co-marketed by Biogen and Genentech in the U.S., by Hoffmann-La Roche in Canada and the European Union, Chugai Pharmaceuticals, Zenyaku Kogyo in Japan and AryoGen in Iran.

Reference
Wiki: Ramos-Burkitt lymphoma

    A hemolytic anemia that is characterized by deficiency of Rh antigens, has_material_basis_in homozygous or compound heterozygous mutation in the RHAG gene on chromosome 6p12.

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DiseaseOntology: Rh deficiency syndrome

    Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated. Risk factors include getting older, being male, smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes for which treatments and outcomes may vary. The first-line treatment of AML is usually chemotherapy, with the aim of inducing remission. People may then go on to receive additional chemotherapy, radiation therapy, or a stem cell transplant. The specific genetic mutations present within the cancer cells may guide therapy, as well as determine how long that person is likely to survive. In 2015, AML affected about one million people, and resulted in 147,000 deaths globally. It most commonly occurs in older adults. Males are affected more often than females. The five-year survival rate is about 35% in people under 60 years old and 10% in people over 60 years old. Older people whose health is too poor for intensive chemotherapy have a typical survival of five to ten months. It accounts for roughly 1.1% of all cancer cases, and 1.9% of cancer deaths in the United States.

Reference
Wiki: secondary acute myeloid leukemia

    Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections. It causes severe pyogenic infections. It can be caused by autosomal dominant inheritance of the ELANE gene, autosomal recessive inheritance of the HAX1 gene. There is an increased risk of leukemia and myelodysplastic cancers. Most cases of SCN respond to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count and decreases the severity and frequency of infections. Although this treatment has significantly improved survival, people with SCN are at risk of long-term complications such as hematopoietic clonal disorders (myelodysplastic syndrome, acute myeloid leukemia). Kostmann disease (SCN3), the initial subtype recognized, was clinically described in 1956. This type has an autosomal recessive inheritance pattern, whereas the most common subtype, SCN1, shows autosomal dominant inheritance.

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Wiki: Severe congenital neutropenia

    A sickle cell disease that is characterized by the replacement of both of the beta-globin subunits in hemoglobin with hemoglobin S, resulting in a low number of red blood cells, repeated infections, and periodic episodes of pain.

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DiseaseOntology: Sickle cell anemia

    Sickle cell disease (SCD), also simply called sickle cell, is a group of hemoglobin-related blood disorders typically inherited. The most common type is known as sickle cell anemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads to a rigid, sickle-like shape under certain circumstances. Problems in sickle cell disease typically begin around 5 to 6 months of age. A number of health problems may develop, such as attacks of pain (known as a sickle cell crisis) in joints, anemia, swelling in the hands and feet, bacterial infections, dizziness and stroke. Long-term pain may develop as people get older. The average life expectancy in the developed world is 40 to 60 years. It often gets worse within age. All the major organs are affected by sickle cell disease. The liver, heart, kidneys, gallbladder, eyes, bones, and joints also can suffer damage from the abnormal functions of the sickle cells, and their inability to flow through the small blood vessels correctly. Sickle cell disease occurs when a person inherits two abnormal copies of the ¦Â-globin gene (HBB) that makes haemoglobin, one from each parent. This gene occurs in chromosome 11. Several subtypes exist, depending on the exact mutation in each haemoglobin gene. An attack can be set off by temperature changes, stress, dehydration, and high altitude. A person with a single abnormal copy does not usually have symptoms and is said to have sickle cell trait. Such people are also referred to as carriers. Diagnosis is by a blood test, and some countries test all babies at birth for the disease. Diagnosis is also possible during pregnancy. The care of people with sickle cell disease may include infection prevention with vaccination and antibiotics, high fluid intake, folic acid supplementation, and pain medication. Other measures may include blood transfusion and the medication hydroxycarbamide (hydroxyurea). In 2023, new gene therapies were approved. A small percentage of people can be cured by a transplant of bone marrow cells. As of 2015, about 4.4 million people have sickle cell disease, while an additional 43 million have sickle cell trait. Sickle cell disease (SCD) affects millions of people worldwide, with a higher prevalence in sub-Saharan Africa, Spanish-speaking regions in the Western Hemisphere (South America, the Caribbean, and Central America), Saudi Arabia, India, and Mediterranean countries like Turkey, Greece, and Italy. In 2015, it resulted in about 114,800 deaths. The condition was first described in the medical literature by American physician James B. Herrick in 1910. In 1949, its genetic transmission was determined by E. A. Beet and J. V. Neel. In 1954, the protective effect against malaria of sickle cell trait was described.

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Wiki: Sickle-cell disease

    A microcytic anemia where the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes).

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DiseaseOntology: Sideroblastic anemia

    Spherocytosis is the presence of spherocytes in the blood, i.e. erythrocytes (red blood cells) that are sphere-shaped rather than bi-concave disk shaped as normal. Spherocytes are found in all hemolytic anemias to some degree. Hereditary spherocytosis and autoimmune hemolytic anemia are characterized by having only spherocytes.

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Wiki: Spherocytosis

    Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li¨CFraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically Acute lymphoblastic leukemia based on blood tests and bone marrow examination. Acute lymphoblastic leukemia is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy typically over a number of years. Treatment usually also includes intrathecal chemotherapy since systemic chemotherapy can have limited penetration into the central nervous system and the central nervous system is a common site for relapse of acute lymphoblastic leukemia. Treatment can also include radiation therapy if spread to the brain has occurred. Stem cell transplantation may be used if the disease recurs following standard treatment. Additional treatments such as Chimeric antigen receptor T cell immunotherapy are being used and further studied. Acute lymphoblastic leukemia affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. Acute lymphoblastic leukemia is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%).

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Wiki: T-cell acute lymphoblastic leukemia

    T-cell acute lymphoblastic leukemia (T-ALL) is a type of acute lymphoblastic leukemia with aggressive malignant neoplasm of the bone marrow. Acute lymphoblastic leukemia (ALL) is a condition where immature white blood cells accumulate in the bone marrow, subsequently crowding out normal white blood cells and create build-up in the liver, spleen, and lymph nodes. The two most common types of ALL are B-lymphocytes and T-lymphocytes, where the first protects the body against viruses and bacteria through antibody production which can directly destroy target cells or trigger others to do so, whilst the latter directly destroy bacteria or cells infected with viruses. Approximately 20% of all ALL patients are categorized specifically to suffer from T-ALL and it is seen to be more prevalent in the adult population in comparison to children, with incidences shown to diminish with age. Amongst T-ALL cases in the pediatric population, a median onset of age 9 has been identified and the disease is particularly prominent amongst adolescents. The disease stems from cytogenic and molecular abnormalities, resulting in disruption of developmental pathways controlling thymocyte development, tumor suppressor development, and alterations in control of cell growth and proliferation. Distinct from adult T-cell leukemia where T-cell lymphotropic virus Type I causes malignant maturation of T-cells, T-ALL is a precursor for lymphoid neoplasm. Its clinical presentation most commonly includes infiltration of the central nervous system (CNS), and further identifies mediastinal mass presence originating from the thymus, along with extramedullary involvement of multiple organs including the lymph node as a result of hyperleukocytosis.

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Wiki: T-cell acute lymphocytic leukemia

    Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role of the virus in the cause of the neoplasm. A small amount of HTLV-1 individuals progress to develop ATL with a long latency period between infection and ATL development. ATL is categorized into 4 subtypes: acute, smoldering, lymphoma-type, chronic. Acute and Lymphoma-type are known to particularity be aggressive with poorer prognosis. Globally, the retrovirus HTLV-1 is estimated to infect 20 million people per year with the incidence of ATL approximately 0.05 per 100,000 per year with endemic regions such as regions of Japan, as high as 27 per 100,000 per year. However, cases have increased in non-endemic regions with highest incidence of HTLV-1 in southern/northern islands of Japan, Caribbean, Central and South America, intertropical Africa, Romania, northern Iran. ATL normally occurs around the age of 62 years but median age at diagnosis does depend on prevalence of the HTLV-1 infection in the geographic location. Current treatment regiments for ATL are based on clinical subtype and response to initial therapy. Some therapy modalities for treatment may not available in all countries therefore strategies differ across the world. All patients are referred to clinical trials if available. Beyond clinical trials, treatments are centered on multiagent chemotherapy, zidovudine plus interferon a (AZT/IFN), and allogenic hematopoietic stem cell transplantation (alloHSCT).

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Wiki: T-cell leukemia

    Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia.[1] The opposite is lymphocytosis, which refers to an excessive level of lymphocytes.

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Wiki: T-cell lymphopenia

    T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include T-cell chronic lymphocytic leukemia, "knobby" type of T-cell leukemia, and T-prolymphocytic leukemia/T-cell lymphocytic leukemia.

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Wiki: T-prolymphocytic leukemia

    A hypolipoproteinemia that is characterized by markedly reduced levels of plasma high density lipoproteins resulting in tissue accumulation of cholesterol esters and that has_material_basis_in homozygous or compound heterozygous mutation in the ABCA1 gene on chromosome 9q31.

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DiseaseOntology: Tangier disease

    Thrombocythemia, or thrombocytosis, is a myeloproliferative disorder characterized by excessive platelet production resulting in increased numbers of circulating platelets. Thrombocythemia can be associated with thrombotic or hemorrhagic episodes and occasional leukemic transformation (summary by Wiestner et al., 1998).

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OMIM: Thrombocythemia

    In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets/microliter (¦ÌL) of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000/¦ÌL. Thrombocytopenia can be contrasted with the conditions associated with an abnormally high level of platelets in the blood ¨C thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known).

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Wiki: Thrombocytopenia

    Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who have an episode of thrombosis (such as deep vein thrombosis in the leg) that was not provoked by other causes. A significant proportion of the population has a detectable thrombophilic abnormality, but most of these develop thrombosis only in the presence of an additional risk factor. There is no specific treatment for most thrombophilias, but recurrent episodes of thrombosis may be an indication for long-term preventive anticoagulation. The first major form of thrombophilia to be identified by medical science, antithrombin deficiency, was identified in 1965, while the most common abnormalities (including factor V Leiden) were described in the 1990s.

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Wiki: Thrombophilia

    Thrombosis (from Ancient Greek ¦È¦Ñ?¦Ì¦Â¦Ø¦Ò¦É? thr¨®mb¨­sis "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus. Thrombosis may occur in veins (venous thrombosis) or in arteries (arterial thrombosis). Venous thrombosis (sometimes called DVT, deep vein thrombosis) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery (ischemia and necrosis). A piece of either an arterial or a venous thrombus can break off as an embolus, which could then travel through the circulation and lodge somewhere else as an embolism. This type of embolism is known as a thromboembolism. Complications can arise when a venous thromboembolism (commonly called a VTE) lodges in the lung as a pulmonary embolism. An arterial embolus may travel further down the affected blood vessel, where it can lodge as an embolism.

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Wiki: Thrombosis

    Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome (USS), is a rare autosomal recessive thrombotic microangiopathy (TMA). Clinically, acute phases of TTP are defined by microangiopathic mechanical hemolytic anemia, severe thrombocytopenia, and visceral ischemia. Hereditary TTP makes up 5% of TTP cases and is caused mostly by biallelic mutation in the ADAMTS13 gene, or in very rare cases, by monoallelic ADAMTS13 mutation associated with a cluster of single-nucleotide polymorphisms (SNPs); most cases of all TTP (95%) are acquired via an autoimmune mechanism (see 188030). Hereditary TTP is more frequent among child-onset TTP compared with adult-onset TTP, and its clinical presentation is significantly different as a function of its age of onset. Child-onset TTP usually starts in the neonatal period with hematological features and severe jaundice. In contrast, almost all cases of adult-onset hereditary TTP are unmasked during the first pregnancy of a woman whose disease was silent during childhood (summary by Joly et al., 2018).

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OMIM: Thrombotic thrombocytopenic purpura

    A thymoma is a tumor originating from the epithelial cells of the thymus that is considered a rare malignancy. Thymomas are frequently associated with neuromuscular disorders such as myasthenia gravis; thymoma is found in 20% of patients with myasthenia gravis. Once diagnosed, thymomas may be removed surgically. In the rare case of a malignant tumor, chemotherapy may be used.

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Wiki: Thymoma

    Upshaw¨CSchulman syndrome (USS) is the recessively inherited form of thrombotic thrombocytopenic purpura (TTP), a rare and complex blood coagulation disease. USS is caused by the absence of the ADAMTS13 protease resulting in the persistence of ultra large von Willebrand factor multimers (ULVWF), causing episodes of acute thrombotic microangiopathy with disseminated multiple small vessel obstructions. These obstructions deprive downstream tissues from blood and oxygen, which can result in tissue damage and death. The presentation of an acute USS episode is variable but usually associated with thrombocytopenia, microangiopathic hemolytic anemia (MAHA) with schistocytes on the peripheral blood smear, fever and signs of ischemic organ damage in the brain, kidney and heart.

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Wiki: Upshaw-Schulman syndrome

    A bone development disease that is characterized by softening and weakening of the bones, hypocalcemia, high levels of parathyroid hormone and hypophosphatemia.

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DiseaseOntology: vitamin D-dependent rickets

    Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions.[1] It arises from a deficiency in the quality or quantity of von Willebrand factor (VWF), a multimeric protein that is required for platelet adhesion. It is known to affect several breeds of dogs as well as humans. The three forms of VWD are hereditary, acquired, and pseudo or platelet type. The three types of hereditary VWD are VWD type 1, VWD type 2, and VWD type 3. Type 2 contains various subtypes.[2] Platelet type VWD is also an inherited condition.[3]

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Wiki: Von Willebrand disease

    X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection. As the form of agammaglobulinemia that is X-linked, it is much more common in males. In people with XLA, the white blood cell formation process does not generate mature B cells, which manifests as a complete or near-complete lack of proteins called gamma globulins, including antibodies, in their bloodstream. B cells are part of the immune system and normally manufacture antibodies (also called immunoglobulins), which defend the body from infections by sustaining a humoral immunity response. Patients with untreated XLA are prone to develop serious and even fatal infections. A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development (at the pre-B cell to immature B cell stage) and a reduced immunoglobulin production in the serum. Btk is particularly responsible for mediating B cell development and maturation through a signaling effect on the B cell receptor BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births and a frequency of about 1 in 100,000 male newborns. It has no ethnic predisposition. XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies. XLA is caused by a mutation on the X chromosome (Xq21.3-q22) of a single gene identified in 1993 which produces an enzyme known as Bruton's tyrosine kinase, or Btk. XLA was first characterized by Dr. Ogden Bruton in a ground-breaking research paper published in 1952 describing a boy unable to develop immunities to common childhood diseases and infections. It is the first known immune deficiency, and is classified with other inherited (genetic) defects of the immune system, known as primary immunodeficiency disorders.

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Wiki: X-linked agammaglobulinemia

    XLTDA is an X-linked recessive hematologic disorder characterized by thrombocytopenia and abnormal platelet morphology and function due to defective platelet maturation. Some patients have a variable severity of dyserythropoietic anemia (summary by Millikan et al., 2011).

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OMIM: X-linked dyserythropoietic anemia and thrombocytopenia