About diamond-blackfan anemia

What is diamond-blackfan anemia?

Blackfan-Diamond anemia (BDA) is a rare blood disorder that is caused by a failure of the bone marrow to generate enough red blood cells. It is characterized by deficiency of red blood cells at birth (congenital hypoplastic anemia) as well as slow growth, abnormal weakness and fatigue, paleness of the skin, characteristic facial abnormalities, protruding shoulder blades (scapulae), webbing or abnormal shortening of the neck due to fusion of certain bones in the spine (cervical vertebrae), hand deformities, congenital heart defects, and/or other abnormalities. The symptoms and physical findings associated with Blackfan-Diamond Anemia vary greatly from case to case.

What are the symptoms for diamond-blackfan anemia?

Diamond Blackfan anemia is characterized by moderate to severe deficiency of red blood cells (anemia). Sometimes white blood cells and platelets may be lower as well. Symptoms of anemia include rapid heartbeat, pale skin, sleepiness, irritability, poor appetite, and weakness. Approximately ninety percent of affected patients are diagnosed within the first year of life. The diagnosis is generally made by 3-4 months of age.

Approximately one-half of those affected have physical abnormalities, such as small head size; wide-set eyes; flat nose; small, low-set ears; small bottom jaw; recessed or small chin; Cleft palate (an opening in the roof of the mouth with or without a cleft lip – a split in the upper lip); and small, missing or extra thumb(s). The neck may be short due to fused vertebrae and shoulder blades may be prominent. About one-third of affected individuals have Slow growth leading to short stature.

Other features of DBA may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), kidney abnormalities; defects of the heart; and males may have hypospadias (a condition in which the urinary tract does not end at the tip of the penis). Many of these defects may need surgical correction.

A possible complication of DBA is the development of cancer at younger than expected ages. Patients with DBA have developed bone cancer (osteosarcoma), colon cancer, and leukemia (blood cancer called acute myeloid leukemia), among others. The patients are also at risk for a pre-leukemic syndrome called myelodysplastic syndrome which is another disorder caused by the bone marrow not making enough healthy blood cells.

What are the causes for diamond-blackfan anemia?

Diamond Blackfan anemia is caused by changes (mutations) in ribosomal protein genes in about 80-85% of those affected. In the remaining 10-15% of patients, no abnormal genes have yet been identified.

A mutation in the RPS19 gene is the cause of DBA in about 25% of patients. Mutations have also been found in RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, and RPS26, and rarely in RPL15, RPL17, RPL19, RPL26, RPL27, RPL31, RPS15A, RPS20, RPS27, RPS28, RPS29, and TSR2. In a few patients, the disease is caused by a mutation in the GATA1 gene.

DBA caused by the ribosomal protein gene mutation follows autosomal dominant inheritance.

What are the treatments for diamond-blackfan anemia?

When the patient presents with anemia, the usual initial treatment includes a red cell transfusion. If available, transfusions are usually the mainstay of treatment for the first year of life for the anemia of DBA. After the first year patients are started on a course of treatment with corticosteroids. This treatment can initially improve the red blood cell count in approximately 80% of people with DBA.

Red blood transfusions are used for those patients who do not respond to corticosteroid treatment. If the patient remains on chronic transfusion therapy (usually required every 3-4 weeks) then the patient will also require iron chelation. Iron chelation is necessary to unload the extra iron that accumulates when a person receives transfusions. If the iron is not removed then the person can develop iron overload in the heart, liver and endocrine organs and develop heart arrhythmias (abnormal heart rhythms), congestive heart failure, liver abnormalities and cirrhosis, diabetes, hypothyroidism, gonadal dysfunction, and other issues.

Some people have such mild signs and symptoms that they do not require treatment. The only curative treatment for the anemia of DBA is bone marrow/stem cell transplantation. This treatment replaces damaged bone marrow with healthy stem cells from a donor. This can be done using an unaffected sibling or an unrelated donor.

What are the risk factors for diamond-blackfan anemia?

Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual only. In approximately 45% of patients, the mutation is inherited from one affected parent. The remaining patients have no history of the disorder in their family, and develop the disorder because of a new (sporadic) gene mutation. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. The rare TSR2 and GATA1 gene mutations are inherited in affected males only from a mother who is an unaffected carrier.

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