what is diamond blackfan anemia?

Answer 1

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. DBA patients have low red blood cell counts (anemia). The rest of their blood cells (the platelets and the white blood cells) are normal. A variety of other congenital abnormalities may also occur.

Diamond-Blackfan anemia is characterized by anemia (low red blood cell counts) with decreased erythroid progenitors in the bone marrow. This usually develops during the neonatal period. About 47% of affected individuals also have a variety of congenital abnormalities, including craniofacial malformations, thumb or upper limb abnormalities, cardiac defects, urogenital malformations, and cleft palate. Low birth weight and generalized growth retardation are sometimes observed. DBA patients have a modest risk of developing leukemia and other malignancies.

A diagnosis of DBA is made on the basis of anemia, low reticulocyte (immature red blood cells) counts, and diminished erythroid precursors in bone marrow. Features that support a diagnosis of DBA include the presence of congenital abnormalities, macrocytosis, elevated fetal hemoglobin, and elevated adenosine deaminase levels in red blood cells. Most patients are diagnosed in the first two years of life. However, some mildly affected individuals only receive attention after a more severely affected family member is identified. About 20-25% of DBA patients may be identified with a genetic test for mutations in the RPS19 gene.

Approximately 10-25% of DBA cases have a family history of disease, and most pedigrees suggest an autosomal dominant mode of inheritance. The disease is characterized by genetic heterogeneity, with current evidence supporting the existence of at least three genes mutated in DBA. In 1997, a patient was identified who carried a rare balanced chromosomal translocation involving chromosome 19 and the X chromosome. This suggested that the affected gene might lie in one of the two regions that were disrupted by this cytogenetic anomaly. Linkage analysis in affected families also implicated this region in disease, and led to the cloning of the first DBA gene. About 20-25% of DBA cases are caused by mutations in the ribosome protein S19 (RPS19) gene on chromosome 19 at cytogenetic position 19q13.2. Interestingly, some previously undiagnosed relatives of DBA patients were found to carry mutations. These patients also had increased adenosine deaminase levels in their red blood cells but no other overt signs of disease. A subsequent study of families with no evidence of RPS19 mutations determined that 18 of 38 families showed evidence for involvement of an unknown gene on chromosome 8 at 8p23.3-8p22. The precise genetic defect in these families has not yet been delineated. In a further 7 families, both the chromosome 19 and chromosome 8 loci could be excluded for involvement, suggesting the existence of at least one other DBA locus in the human genome.

The phenotype of DBA patients suggests a hematological stem cell defect specifically affecting the erythroid progenitor population. This is difficult to reconcile with the known function of the single known DBA gene. The RPS19 protein is involved in the production of ribosomes. As such, loss of RPS19 function would be predicted to affect translation and protein biosynthesis and have a much broader impact. Disease features may be related to the nature of RPS19 mutations. The disease is characterized by dominant inheritance, and therefore arises due to a partial loss of RPS19 protein function. It is possible that erythroid progenitors are acutely sensitized to this decreased function, while most other tissues are unaffected.

Corticosteroids can be used to treat anemia in DBA. In a large study of 225 patients, 82% initially responded to this therapy, although many side effects were noted. Some patients remained responsive to steroids, while efficacy waned in others. Blood transfusions can also be used to treat severe anemia in DBA. Periods of remission may occur, during which transfusions and steroid treatments are not required. Bone marrow transplantation (BMT) can cure hematological aspects of DBA. This option may be considered when patients become transfusion-dependent because frequent transfusions can lead to iron overloading and organ damage. However, data from a large DBA patient registry indicated that adverse events in transfusion-dependent patients were more frequently caused by BMTs than iron overloading.

Answer 2

In Blackfan Diamond (or Diamond Blackfan) anemia the body's bone marrow produces little or no red blood cells. A person is born with it. It affects approximately 600 - 700 people worldwide. Its cause is unknown, although a genetic error on Chromosome 19 is associated with about 25% of cases. In about 10-20% of cases, there is a family history of the disorder.

Answer 3

In Blackfan Diamond (or Diamond Blackfan) anemia the body's bone marrow produces little or no red blood cells. A person is born with it. It affects approximately 600 - 700 people worldwide. Its cause is unknown, although a genetic error on Chromosome 19 is associated with about 25% of cases. In about 10-20% of cases, there is a family history of the disorder.
What are the symptoms?
Blackfan Diamond anemia can be difficult to identify. In about one-third of children born with the disorder there are physical defects such as hand deformities or heart defects, but a clear set of signs hasn't been identified. The symptoms may also vary greatly, from very mild to severe and life-threatening.

Red blood cells carry oxygen throughout the body, so a child with Blackfan Diamond may have symptoms related to not enough blood oxygen (anemia):

pallor (paleness)
irregular heartbeat, due to the heart trying to keep oxygen moving throughout the body
fatigue, irritability, and fainting