Description

Blackfan-Diamond disease (ADB) is a congenital, often macrocytic, arygenerative anemia associated with ertitroblastopenia. The annual incidence in the whole European population is approximately 1 / 150,000. It can affect both sexes and no particular ethnic predispositions have been observed. It usually appears within 2 years; the diagnosis after 4 years is unlikely. The main signs are pallor and dyspnea, especially during breastfeeding or feeding. Pallor is sporadic, organomegaly is not found and the clinical signs point to hemolysis or the involvement of hematopoietic cells. Over half of patients have short stature and congenital anomalies, especially skull-facial (Pierre Robin’s syndrome and cleft palate, see these terms), thumb and urogenital anomalies. Pregnancy in affected women carries a high risk for both the mother and the newborn. Affected subjects are at high risk for leukemia and cancer. Blackfan-Diamond disease is transmitted in an autosomal dominant manner with variable penetrance. The mutations responsible for the disease were characterized in 40-45% of cases. The genes involved encode ribosomal proteins (RPs), both for small ribosomal subunits (RPS7, RPS17, RPS19, RPS24), and for large ones (RPL5, RPL11, RPL35A). Mutations in the RPS19, RPL5 and RPL11 genes are present in 25%, 9% and 6.5% of patients respectively, while mutations in the other genes have only been reported in between 1% and 3% of cases. Up to now, the only delineate genotype-phenotype correlation concerns the recurrence of craniofacial defects in the carriers of mutations in the RPL5 and RPL11 genes and their rarity in the carriers of mutations in the RPS19 gene. In a child with anemia and erythroblastopenia, the diagnosis can be supported by a positive family history (10-20% of cases), associated malformations (40% of cases), and increased erythrocyte adenosine deaminase (ADA), which it is a common, but not specific, sign and may also be present in clinically asymptomatic parents. The detection of a mutation in a gene-disease has diagnostic value. The differential diagnosis arises with transient erythroblastopenia (see this term), chronic parvovirus B19 infection and other congenital anemias. Genetic counseling and prenatal diagnosis are complex due to the variability of clinical symptoms and due to the fact that only in 40-45% of affected individuals has been identified a mutation in the RP gene. In family cases the risk of transmission is 50%. Ultrasound follow-up is recommended in pregnancies at risk. The main therapies include transfusions at regular intervals and long-term therapy with corticosteroids. The treatment must be adapted in individual patients and must be chosen based on their age. Steroids should be avoided in the first year of life. The short stature is due in part to the syndrome and partly to complications arising from the therapy (steroids, hemochromatosis). Allogeneic bone marrow transplantation should be considered in corticosteroid subjects, when there is a brother / sister, unaffected, identical HLA. The prognosis is generally good. However, life expectancy is reduced in the presence of complications secondary to therapy and because of the high incidence of cancer. The severity of the disease depends on the therapy and the patient’s response. The quality of life in patients who regularly undergo transfusions is obviously altered.

External Information

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