CDA I: Clinically, the spectrum ranges from mild to severe. In approximately half
of the cases, the diagnosis is made in the neonatal period secondary to
significant anemia. In the other half, the diagnosis is commonly made later
in childhood or adolescence secondary to mild anemia with intermittent
jaundice, splenomegaly, and sometimes hepatomegaly. The hemoglobin level
typically stays at around 90 g/liter (range 66-116 g/liter), so transfusions are
rarely required. Macrocytosis may be present, and the reticulocyte count is
normal or low. The peripheral blood smear shows anisocytosis
(elliptocytosis) and poikilocytosis with dacryocytosis. Serum concentration
of bilirubin is elevated, while haptoglobin is decreased. Iron overload
(even without transfusions) may result in hepatic cirrhosis and skin and
endocrine changes. Biliary complications (e.g., bile duct obstruction,
pancreatitis, bile peritonitis) may lead to sepsis. Bone marrow aspirate
reveals erythroid hyperplasia with significantly dysplastic nuclei (irregular,
karyorrhectic, binucleate, trinucleate appearance). Long chromatin strands
surrounded by microtubules forming intercellular bridges and connecting the
nuclei of two otherwise almost separated cells are considered typical for
CDA I (although it may be seen in other forms of CDA). Erroneously, a
β-thalassemia trait can be mimicked by increased percentage of
hemoglobin A2 and the α/non-α-globin chain synthesis
ratio. Severe forms, usually occurring before or at birth with hemoglobin
levels as low as 30 g/liter requiring regular transfusions, have been
described. Occasionally, the presenting features are dysmorphic body signs
rather than anemia related and may include short stature, platyspondyly,
hypoplastic ribs, hearing loss, hypertelorism, micrognathia, large mouth,
thick lips, large ears, syndactyly, aplasia/hypoplasia of distal phalanges,
onychodysplasia, and brown skin patches. These patients may be on
interferon-α therapy.