The Diamond Blackfan Anemia Registry: Tool for Investigating the Epidemiology and Biology of Diamond—Blackfan Anemia

Abstract

Diamond-Blackfan anemia (DBA) is a heterogeneous genetic disorder characterized by red cell aplasia and congenital anomalies. One of what appears to be multiple DBA genes has been cloned. Affected individuals in the same family may vary dramatically as to the degree of anemia, response to corticosteroids, and the presence of congenital anomalies. The epidemiology of DBA has been gleaned largely from literature reviews. This approach is limited because of the two-fold disadvantage of the reporting bias inherent in the literature and the lack of an active patient database. The Diamond Blackfan Anemia Registry of North America (DBAR) is designed to overcome these disadvantages to study the epidemiology and biology of DBA. The DBAR is a comprehensive database of patients with DBA who are enrolled after informed consent is obtained. Identification of patients is made through outreach to pediatric and adult hematologists and the Diamond Blackfan Anemia Foundation. The patients and/or their families complete a detailed questionnaire. A review of medical records and telephone interviews are performed to complete and clarify the information provided. To date, 354 patients have been enrolled in the DBAR. Using this database, important epidemiologic, clinical, and laboratory observations have been made with regard to the clinical presentation, the inheritance of DBA, the genetics of congenital malformations, the therapeutic outcome, including the efficacy of hematopoietic stem cell transplantation, and the recognition of DBA as a cancer predisposition syndrome. In particular, the database is an essential substrate for DBA gene discovery.

Diamond-Blackfan anemia: erythropoiesis lost in translation

“…1 Although not yet statistically validated, patients with DBA also seem to have an increased risk of acute myeloid leukemia (AML) and a wide variety of nonhematopoietic tumors, for example, osteogenic sarcomas. 1,[8][9][10] The main differential diagnosis is transient erythroblastopenia of childhood. 6,11 After confirmed diagnosis of DBA, the initial therapeutic regimen consists of blood transfusions followed by corticosteroid treatment.…”

Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia

“…Congenital abnormalities, including craniofacial, cardiac, genitourinary, and upper limb/hand malformations, are found in 40% to 50% of patients. 5,6 In addition to anemia and abnormalities of embryogenesis, DBA is associated with an increased risk of cancer, most commonly hematologic malignancies and osteogenic sarcoma. 5,7 Approximately 25% of affected patients have heterozygous alterations of RPS19, which encodes a protein component of the small ribosomal subunit.…”

“…5,6 In addition to anemia and abnormalities of embryogenesis, DBA is associated with an increased risk of cancer, most commonly hematologic malignancies and osteogenic sarcoma. 5,7 Approximately 25% of affected patients have heterozygous alterations of RPS19, which encodes a protein component of the small ribosomal subunit. 8 Haploinsufficiency of the RPS19 gene product has been demonstrated in a subset of cases 9 and appears to be sufficient to cause DBA.…”

Study of 22 Egyptian Patients With Diamond-Blackfan Anemia, Corticosteroids, and Cyclosporin Therapy Results

“…14 An incidence of 4 to 5 cases per million live births was reported. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Although most cases are sporadic, inheritance is observed in 10% of patients, with a dominant or, more rarely, recessive pattern. 8 -16 Abnormalities in chromosome 19q13.2 have been identified in 25% of familial and sporadic cases of DBA, in another subset of patients another locus on chromosome 8p has identified in association with DBA.…”