Diamond Blackfan Anemia Registry (DBAR)

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.

Inclusion Criteria:

- Patients must meet the diagnostic criteria for DBA which include the following:

1. Normochromic, usually macrocytic and occasionally normocytic anemia developing
early in childhood

2. Reticulocytopenia

3. Normocellular bone marrow with a selective deficiency of red cell precursors

4. Normal or slightly decreased leukocyte count

5. Normal or often increased platelet count

6. Or, a confirmed mutation in one of the identified DBA genes

Exclusion Criteria:

- Any subject identified as having another bone marrow failure syndrome (eg. Fanconi
anemia, dyskeratosis congenita, Shwachman Diamond syndrome, etc.) will be excluded.