Congenital hypoplastic anemia manifesting in the first
year of life. Increased risk for leukemia.
Seven-month-old boy with Blackfan-Diamond syndrome has anomalies of the
ear and a short neck because of fusion of the cervical vertebrae.
Diamond-Blackfan Anemia; Congenital Hypoplastic Anemia;
Congenital Pure Red Cell Anemia/ Aplasia; Chronic Congenital Aregenerative
Anemia; Chronic Erythroblastopenia; Constitutional Erythroid Hypoplasia;
Erythrogenesis Imperfecta; Estren-Dameshek Variant of Fanconi Anemia.
First described in 1938 by the two American pediatricians Kenneth Daniel Blackfan and
Louis Klein Diamond.
Several hundred cases have been reported in the
literature. Annual incidence is approximately 5:1,000,000 live births.
Most often autosomal dominant, but autosomal
recessive transmission with normal chromosomes has been described (parental
consanguinity is a risk factor). Approximately 25% of cases can be linked
to a mutation of the ribosomal protein S19 (RBS19) with gene map locus
19q13.3. The function of this protein has not been elucidated.
Uncertain, but may be secondary to a defect of
pluripotent stem cell differentiation into erythroid progenitor cells
(response to erythropoietin may be altered).
Typically, the initial signs are pallor and dyspnea
during breast-feeding or bottle feeding. Diagnosis usually is made by 6
months of age (70-90% of patients present by the first 3 months of life, but
only 13% are anemic at birth): severe macrocytic anemia, high hemoglobin
F levels for patient's age, reticulocytopenia (usually <1%), normal white cell count,
and normal-to-elevated platelets. As a consequence of complete cessation of
erythropoiesis, many patients do not have an elevated mean corpuscular
volume initially. However, these patients become macrocytic once recovery of
erythropoiesis occurs. Bone marrow aspiration shows decreased erythroid
precursors with less than 5% of nucleated cells being erythroblasts.
Hepatosplenomegaly may occur in up to 40% of affected children and,
because it is reversible after transfusion, it most likely reflects heart
failure. Although not pathognomonic, increased levels of erythrocyte
adenosine deaminase can frequently be detected. Serum and urine
erythropoietin levels are elevated. Approximately 67% of patients respond
initially to steroids and approximately 40% require regular transfusions.
Allogenic bone marrow transplant may be a therapeutic option for
steroid-resistant patients but remains controversial because the disease is
not malignant and secondary response of these patients to steroids is well
Congenital hypoplastic anemia. Relapse is often
associated with infections. Patients may be transfusion dependent from time
of diagnosis if they are resistant to steroids or become secondarily
transfusion dependent once steroid resistance develops. Chelation therapy
with deferoxamine is often required with chronic transfusions. Associated
anomalies with this disease occur in approximately 40% of patients and
may include growth retardation, facial abnormalities (microcephaly or
macrocephaly, wide fontanelle, micrognathia, arched or cleft palate,
macroglossia, thickening of the upper lip), ocular abnormalities
(microphthalmos, strabismus, hypertelorism, epicanthal folds, blue sclerae,
cataracts, glaucoma), thumb abnormalities (absent, bifid, subluxed,
supernumerary), and renal abnormalities (absent, duplicated, or horseshoe kidneys).
Other symptoms and findings include congenital heart defects, abnormal
weakness and fatigue, pale skin, protruding scapulae, and webbing or
abnormal shortening of the neck because of fused cervical vertebrae.
Check hematocrit and transfuse as
needed. Check for systemic signs of iron overload, specifically hepatic
fibrosis/cirrhosis and myocardial failure. Check hepatic and renal function
(laboratory, ultra-sound). Evaluate possibility of difficult tracheal
Maintain oxygen-carrying capacity.