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Glossary |
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The diagnosis of aplastic anemia is based on the finding of low blood counts with an empty marrow. In addition, your doctor will need to rule out other diseases or inherited causes of low blood counts, since those disorders require different therapies. Aplastic anemia may be cured by a hematopoietic stem cell transplant (HSCT) from a matched sibling donor. A bone marrow transplant from a matched unrelated donor, cord blood, or other family member may be considered under certain circumstances. Acquired aplastic anemia may also be treated with strong immunosuppressive medications, typically ATG (anti-thymocyte globulin, or antibodies against human thymocytes) given intravenously in the hospital over 4 days, and cyclosporin given orally over many months.
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This illness first affects the platelets. It is most often diagnosed in early childhood and starts with bruising, bleeding, and tiny spots of bleeding into the skin called "petechiae." Amegakaryocytic thrombocytopenia is caused by a mutation on the MPL gene. The disease is autosomal recessive; it occurs only if a gene is inherited from each parent. This disease affects males and females equally. It can proceed to aplastic anemia when the red and white blood cells also become abnormally low because the bone marrow becomes empty. Patients with this condition are predisposed to developing leukemia, a cancer of the blood and bone marrow. In some cases, hematopoietic stem cell transplant (HSCT) may treat this condition.
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This disorder is characterized by episodic increasing and decreasing neutrophil, or white blood cell counts. The neutrophil counts fall to low levels for several days at regular intervals, usually every 3-4 weeks. During this time, the patient may experience fevers, mouth sores (aphthous ulcers or canker sores), and are at increased risk for infection. If symptoms are severe or if the patient has a history of recurrent or serious infections, G-CSF, a hematopoietic growth factor, may be given. G-CSF does not prevent the changes in neutrophil counts, but may prevent the counts from dipping too low and may ameliorate symptoms. There is an increased risk of leukemia with this disorder.
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This syndrome was originally described by Drs. Diamond and Blackfan, two physicians at Children’s Hospital Boston. This form of anemia causes low red blood cell levels. Some patients with Diamond-Blackfan anemia may also have congenital abnormalities such as short stature and malformed thumbs. Most patients are diagnosed before age one. Mutations of at least nine ribosomal protein (RP) genes, such as RPS19, have been linked to this disease, and all are inherited (in 40-45% patients) as an autosomal dominant (one parent affected). RPS19 is a component of the ribosome, which is part of the protein synthesizing machinery of the cell. RPS19 gene mutations may be inherited or may arise spontaneously in the affected patient. Mutations in several other RP genes also cause DBA, and unidentified genes still account for about half of the cases. Research to identify the other genes is ongoing, and most of the new DBA genes were discovered at Children's. Patients with Diamond-Blackfan anemia are at risk for developing leukemia (cancer of the blood and bone marrow) and sarcomas.
If treatment is required, options typically consist of red cell transfusions or a type of steroid called prednisone which is a medicine that is taken by mouth. Some patients may benefit from a hematopoietic stem cell transplant.
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This disorder is classically characterized by the development of abnormal fingernails and toenails (dyskeratosis), a lacy rash on the face, neck, and chest, and white patches (leukoplakia) in the mouth. These symptoms are typically not present at birth but develop during childhood. Other symptoms may include thin bones (osteoporosis), abnormal teeth, dry eyes/mouth, thin hair, thickened palms, and immune dysfunction. This disease is much more common in males, and about half the people with the disorder develop bone marrow failure. Six genes, including DKC1, hTERC and TINF2 have been identified for this disorder, but more, as yet unidentified, are thought to be involved. DKC1 is X-linked, meaning that the disease is generally only seen in boys. The gene hTERC leads to dyskeratosis congenita in an autosomal dominant fashion, meaning that only one copy of an affected gene is required to develop the disease in either boys or girls. People with Dyskeratosis congenita are prone to develop head and neck cancers (tongue, mouth, and throat); gastrointestinal cancers of the esophagus, stomach, colon, and rectum, and leukemia, or cancer of the blood and bone marrow. They may also develop lung problems including pulmonary fibrosis. Female carriers of the X-linked form of this disorder are still potentially at risk for cancer development and should be regularly monitored.
Hematopoietic stem cell transplant (HSCT) can treat the bone marrow failure in this disorder but may be associated with significant risk of side effects, so risks and benefits must be carefully weighed in each case. Other medicines that may be used to increase the blood counts are hematopoietic growth factors and androgens.
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Hematopoietic stem cell transplant (HSCT) can treat the bone marrow failure in this disorder but may be associated with significant risk of side effects, so risks and benefits must be carefully weighed in each case. Other medicines that may be used to increase the blood counts are hematopoietic growth factors and androgens.
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This disease, usually diagnosed in the first or second decade, almost always leads to aplastic anemia, when the body makes insufficient supplies of all blood cells - red and white cells and platelets. Although some patients with the illness may have no other symptoms, Fanconi anemia may also be associated with:
- Short stature
- Brown birth marks (cafe au lait spots) or light spots (ash leaf spots)
- Abnormal thumbs, often including abnormalities in the bones between the elbow and wrist
- Kidney, bladder or ureter abnormalities
- Heart Defects
- Gastrointestinal abnormalities
- Endocrine abnormalities
- Middle and outer ear abnormalities with loss of hearing
At least twelve different genes are responsible for Fanconi anemia. The disease is diagnosed using a chromosome breakage test, which measures the amount of damage to chromosomes after exposure to specific drugs (mitomycin C or diepoxybutane). In addition, sophisticated genetic analysis of the particular gene mutation may be performed(called complementation or DNA sequencing). Fanconi anemia only occurs if the child inherits an abnormal gene from each parent. This disease affects both boys and girls.
Fanconi anemia can cause cancers including:
- Leukemia (cancer of the blood/bone marrow)
Solid organ cancers including:
- Head and neck cancer (mouth, tongue and throat)
- Gynecologic cancers (particularly labial, ano-genital and cervical cancer)
- Gastrointestinal cancers (especially cancer of the esophagus)
- Brain tumors
Some patients are diagnosed as adults when they develop cancer as their first sign of Fanconi anemia. These cancers tend to develop at a much younger age than in the general population and may be recurrent. Patients may experience excessive side effects of chemotherapy or radiation used to treat the cancers and such treatment should take place only at centers experienced in caring for patients with Fanconi anemia. Hematopoietic stem cell transplant (HSCT) can cure the aplastic anemia, leukemia and leukemia predisposition, but does not cure the solid tumor risk. Patients with Fanconi anemia are particularly susceptible to the side effects of HSCT, so treatment options require careful consideration of risks and benefits for each patient. Medical treatments that may improve the blood counts include androgens and hematopoietic growth factors. Patients must be regularly monitored for early signs of leukemias and solid tumors. Surgical resection of solid tumors is the mainstay of therapy.
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Patients with Pearson syndrome may have short stature, metabolic problems, poor food absorption due to pancreatic insufficiency, low numbers of red cells (macrocytic sideroblastic anemia), white cells, or platelets, and problems with the heart, kidney, liver, or endocrine (hormone) system. The illness is diagnosed through blood counts, characteristic features in the bone marrow, and genetic testing that can identify the genetic mutation (deletions in mitochondrial DNA). Anemia may be treated with red blood cell transfusions. Pancreatic enzyme supplementation may be needed. Metabolic problems may require medications.
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This condition is characterized by very low white cell counts, resulting in serious bacterial infections that usually develop in infancy. There are several forms of severe congenital neutropenia. An autosomal dominant form may be caused by mutations in the ELA2 gene or the GFI1 gene. An X-linked form is caused by activating mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. An autosomal recessive form (also known as Kostmann syndrome) has also been described and the gene causing this syndrome has recently been identified. Severe congenital neutropenia is associated with an increased risk of leukemia (cancer of the blood/ bone marrow). Treatment may consist of hematopoietic growth factors (G-CSF or GM-CSF) for neutropenia or HSCT.
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This disorder was first described by Drs. Shwachman, Oski and Diamond, three physicians at Children's. The characteristic features of Shwachman-Diamond syndrome are pancreatic enzyme deficiency (manifested by fat malabsorption, fatty malodorous stools, poor growth, and deficiencies of vitamin A,D,E, or K) and low blood cell counts (typically white cells, but low numbers of red cells or platelets may also be seen). Patients may have short stature, poor food absorption, and liver or bone abnormalities. The condition can lead to aplastic anemia, myelodysplasia (a pre-leukemic disorder of the bone marrow) and leukemia (cancer of the blood/bone marrow).
Shwachman-Diamond syndrome is diagnosed through tests of pancreas function (which may involve blood and stool samples, or imaging studies of the pancreas), bone marrow tests, and genetic testing which can identify the genetic mutation. One gene causing the disorder in 90 percent of cases has been identified and is called SBDS for Shwachman Bodian Diamond Syndrome. The disease is autosomal recessive and is seen in both boys and girls. There may be additional as yet unidentified genes that cause this disorder.
Pancreatic dysfunction is treated with oral pancreatic enzyme supplements. Bone marrow failure can sometimes be treated with a hematopoietic stem cell transplant (HSCT). Risks and benefits of HSCT must be carefully weighed for each patient. Medical treatment for neutropenia includes hematopoietic growth factors (G-CSF or GM-CSF).
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Patients with this disorder are missing one of the two bones from the lower arm. Bruising, a result of low platelets, may be present at birth. A gene for this disease has not yet been identified. Males and females are affected equally. The diagnosis is made after physical examination and blood tests that reveal low platelet counts due to decreased platelet production. Low platelet counts are treated with platelet transfusions. The platelet count spontaneously improves over time in most patients.
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Other rare forms of bone marrow failure are occasionally seen. These include: ataxia-pancytopenia, cartilage-hair hypoplasia, and Barth syndrome. Other genetic diseases such as Seckel syndrome or Nijmegen Breakage Syndrome may sometimes result in bone marrow failure. This list is not complete, but illustrates some of the additional types of marrow failure that may be seen.
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