(1) usually macrocytic anemia (a decreased number of larger than
     normal red blood cells),
(2) reticulocytopenia (a decreased number of new young red blood cells)
(3) normal bone marrow cellularity, but with a selective deficiency in
     red blood cell precursors
(4) normal or slightly decreased white blood cell count
(5) normal or slightly increased platelet count

• Blackfan Diamond anemia
• congenital pure red cell aplasia
• congenital hypoplastic anemia
• Aase syndrome (felt to be a subset of DBA, and not a distinct disorder)

Initial Treatment
Corticosteroids (prednisone and related drugs) and red blood cell transfusions are the mainstays of therapy.
In the DBAR, the initial patient response to steroids is as follows:
• 82% were initially responsive to steroids
• 16% were non-responsive to initial steroids and required transfusion
• 2% of patients were never treated with steroids

Subsequent Treatment
Overall 44% of patients are currently on corticosteroids.
Steroid-related side effects were observed in many of the patients.
• 40% of patients had Cushingoid features (puffy face, swelling)
• 12% had pathologic fractures (bone fractures occurring with no or minimal trauma)
• 6.8% had cataracts
36% of patients are currently receiving chronic (usually monthly) red cell transfusions. Of these,
• 32% were never steroid responsive (i.e. required transfusions initially because they were non-responsive to steroids)
• 17% became steroid refractory (i.e. had been on steroids but lost the response to steroids over time)
• 49 % could not be weaned to an acceptable dose of steroids (i.e. only had a response to high doses of steroids with too many side effects)
• 1% never received steroid therapy
• 1% are being transfused for reasons unknown

Other Treatments for DBA (see Experimental Treatments )
DBA patients have occasionally responded to treatment with: Interleukin-3 (no longer available), very high doses of corticosteroid, androgens, cyclosporine, and metoclopramide (Reglan). All of these medications have toxicities that must be described by the hematologist prior to their use.

Remission
A “remission” is defined as a stable hemoglobin adequate for age, maintained for at least six months, without any corticosteroids, transfusions or other therapy.
There are 49 patients in the DBAR who are in “remission”. Of these,
• 37 patients had a “remission” from steroid therapy
• 9 patients from transfusion therapy, and
• 3 patients from unknown treatment status
9 patients had recurrence of anemia.
37 patients remitted within the first 10 years of age
10 patients remitted after age 10 years
Thus, 20% of all patients remitted once in their lifetime (most by age 25), with 77% of these patients remitting during the first decade. A single patient entered his first remission at age 38.
Most patients have sustained remissions.

Genetics
The first DBA gene, named DBA1, has been identified as RPS 19, on chromosome 19q13.2. Approximately 20-25% of DBA patients will have a mutation in the DBA1 gene.
A second gene, DBA2, has been localized to chromosome 8p. It has not yet been identified. It is estimated that 40-45% of DBA patients will be shown to have an abnormality in this gene.
The remainder of the patients will have a gene defect in genes yet to be determined.
In the DBAR 7 % of families report having more than one affected individual. Most of these families appear to be of dominant inheritance (meaning transmission from a parent to a child).
Within these families there is great variability in the manifestations (eg. degree of anemia, birth defects, etc.) of DBA. For example, the parent may have mild anemia while the child is steroid or transfusion dependent, or the parent may be steroid responsive while the child does not respond to steroid and is transfusion dependent. Many different combinations within a family have been seen. In addition some affected members may have birth defects while others do not.

Congenital Anomalies (Birth Defects)
47% of the patients in the DBAR have physical abnormalities (not including short stature). Of these,
• 50% of the abnormalities are of the face and head (including cleft lip and palate)
• 38% are of the upper arm and hand
• 39% are of the kidney, and
• 30% of the heart
21% of patients have more than one abnormality.

Stem Cell Transplant Outcomes
Stem cell transplantation (SCT), also known as bone marrow or cord blood transplantation (depending on the donor source), is curative in DBA. However the role of transplantation for patients with DBA remains complex and controversial.
27 patients in the DBAR have undergone a stem cell transplant.
The median age at transplant for all patients was 6 years 10 months.
12 of the 14 HLA-matched sibling donor transplants are alive and well.
Most of the sibling transplants used chemotherapy alone as a conditioning regimen.
3 of the 12 alternative donor transplants are alive.
• 1 patient received bone marrow from a mismatched sibling
• 1 patient received bone marrow from a mismatched parent
• 4 patients received unrelated cord blood, and
• 6 patients received unrelated bone marrow
Most of the alternative donor (mismatched family or unrelated donor) transplants used a combination of chemotherapy with radiation therapy for pre-transplant conditioning.

Cancer Epidemiology
A review of the literature reports cases of leukemia and solid tumors in DBA patients.
10 patients enrolled in the DBAR or their relatives found to have malignancies.
• 4 patients were diagnosed with osteogenic sarcoma (a rare bone tumor)
• 2 patient were diagnosed with myelodysplastic syndrome (leukemia-like illness)
• 2 patients were diagnosed with colon carcinoma
• 1 patient was diagnosed with a soft tissue sarcoma
• 1 patient was diagnosed melanoma
One important feature of DBA-associated cancers is that they present at a younger age than those cancers are usually found. Thus careful analysis of DBA patients and their families is essential to defining the cancer risk in this population.