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.
Blackfan-Diamond anemia is characterized by moderate to severe deficiency of red blood cells. People with Blackfan-Diamond anemia have low red blood cell counts, but their platelet and white cell counts are normal.
Symptoms include abnormal weakness, paleness, and tiredness (lethargy), and they are often first noticed at approximately one month of age. Approximately one-third of those affected have physical anomalies, such as abnormal thumbs, characteristic facial features, or a short neck. Short stature is common.
Facial anomalies may include a snub nose, widely separated eyes, and/or a protruding upper lip. The affected individual’s neck may be webbed or shortened and immobile due to fused vertebrae and shoulder blades may be prominent.
Approximately 30 percent of those affected are diagnosed in the first three months of life. Ninety percent are diagnosed within the first year.
A substantial risk exists for the development of myelodysplastic syndrome or acute myeloid leukemia, as well as selected solid tumors such as osteosarcomas. In rare cases, due to severe anemia, congestive heart failure may occur.
The exact cause of Blackfan-Diamond anemia is not known at this time. There are at least three genes associated with this disorder, but only one has been fully identified at this time.
The gene that has been identified is located on chromosome 19 (19q13.2) and is known as RPS19 (ribosomal protein S19). The disease caused by change (mutation) of this change is inherited in an autosomal dominant pattern. There is some evidence that the disorder may be autoimmune in origin as well.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 19q13.2” refers to band 13.2 on the long arm of chromosome 19. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Blackfan-Diamond anemia is a very rare disorder that affects males and females in equal numbers and is equally represented among all ethnic groups. The incidence of BDA is reported as 7 cases per million of population.
Guidelines for the diagnosis of Blackfan-Diamond anemia have been published by a team of physicians at the Toronto Hospital for Sick Children.
Blackfan-Diamond anemia is usually treated with adrenal corticosteroid drugs beginning as early as possible. Red blood cell transfusions may be used in conjunction with steroid treatments. Multiple blood transfusions can be associated with heart and liver problems, and excessive accumulations of iron in body tissues. Multiple transfusions (every 4-8 weeks) are ordered when the anemia is particularly severe and when the response to treatment with steroids is lee than expected. Infections must be carefully guarded against since they can cause worsening of the blood condition.
The only cure for BDA is bone marrow transplantation. However, finding the matching healthy bone marrow from a willing donor is difficult.
Genetic counseling will be of benefit to patients and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
There are at least eight clinical trials underway (Summer 2006) that are designed to study various aspects of Blackfan-Diamond anemia. For information on the following, contact the NIH Patient Recruitment Office (see above) or visit the www.clinicaltrials.gov web site.
The National Heart Lung and Blood Institute (NHLBI) is sponsoring a study of the use of the drug Rituximab to treat individuals with moderate plastic anemia, pure red cell aplasia, or Diamond-Blackfan anemia. The clinical trials identifier is: NCT00229619.
The National Institute of Diabetes and Digestive and Kidney Diseases is sponsoring a study aimed at improving the results of bone marrow transplantation for patients with severe congenital anemias. The clinical trials identifier is: NCT00061568.
St. Jude Children’s Research Hospital is sponsoring a study of partially matched stem cell transplantation for patients with anemias that are resistant to treatment. The clinical trials identifier is: NCT00244010.
The pharmaceutical company Novartis is sponsoring a trial involving the drug Deferasirox for individuals with congenital disorders of the red blood cells. The clinical trials identifier is: NCT00235391.
The National Cancer Institute (NCI) is sponsoring a genetic study of cancer risk and gene identification in patients with inherited bone marrow disorders and their families. The clinical trial identifier is: NCT00056121.
Dr. Paul J. Orchard of the University of Minnesota is the lead researcher in a study of stem cell transplantation for bone marrow failures. The clinical trial identifier is: NCT00176878.
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