BACKGROUND:
Diamond Blackfan anemia (DBA) is a heterogeneous genetic disorder characterized by pure
red cell aplasia, congenital anomalies, a predisposition to pancytopenia and
myelodysplasia as well as hematopoietic and non-hematopoietic cancer. Anemia usually
presents in infancy or early childhood and greater than 40% of patients have at least one
congenital anomaly. The actuarial cancer risk is, as of yet, undetermined. One DBA gene
has been cloned and the existence of at least two other DBA genes has been inferred by
linkage analysis. Penetrance and expressivity of DBA genes are highly variable.
"Affected" individuals within the same family may vary dramatically as to the degree of
anemia, response to corticosteroids, the presence of congenital anomalies and the
development of cancer. Despite improvements in understanding of this disorder there are
significant deficiencies in knowledge that inhibit the exploitation of this syndrome to
increase both specific and general knowledge of mechanisms of hematopoietic failure,
birth defects and cancer predisposition. Furthermore this disease will, in the near
future, provide a valuable platform to study complex gene interactions. There are less
than 1000 individuals in the United States and Canada estimated to have DBA, representing
at least 11 genotypes. Thus, no single center follows sufficient numbers of
well-characterized patients for meaningful clinical and laboratory investigations.
Furthermore, clinicians require an accurate knowledge of the clinical and laboratory
presentation, mode of inheritance, treatment response, outcomes and prognosis to make
important diagnostic treatment and reproductive decisions. A comprehensive registry that
captures this information and characterizes patients accurately is therefore essential to
advance our understanding of DBA, and in the process, knowledge regarding hematopoietic
cell differentiation, birth defects and cancer predisposition. The registry will be an
essential component of clinical and laboratory DBA related research and patient care.
The Diamond Blackfan Anemia Registry (DBAR) was established in 1992, and families were
asked to participate if a member was affected by the disorder. From this, the Diamond
Blackfan Anemia Foundation (DBAF) was established, largely as a cooperating entity for
families to share information. The registry attempts to establish contact with all
affected individuals at the time of diagnosis, avoiding the pitfalls of reporting bias
inherent to the study of many diseases for which extraordinary events prompt referral to
specialized centers. The registry is already capturing a high percentage of the estimated
number of new cases per year, and has facilitated genetic studies to define the gene(s)
responsible for the disorder. Thus, the registry has an established track record based on
funding from non-NIH sources.
The study is in response to RFA HL-04-008 on Molecular Mechanisms Underlying
Diamond-Blackfan Anemia and Other Congenital Bone Marrow Failure Syndromes.
DESIGN NARRATIVE:
The objective of this study is to expand and update the DBAR in order to: 1) facilitate
investigations into the epidemiology and biology of Diamond Blackfan anemia; 2) provide
an accurate phenotype of DBA patients to facilitate genotype- phenotype correlations; 3)
provide access of well characterized patients to treatment protocols; 4) provide patients
to access to research studies; 5) provide patients with results of research studies; 6)
serve as a resource to patients and their doctors to guide diagnostic, therapeutic, and
reproductive decisions.