Blood Spotlight Congenital dyserythropoietic anemias: molecular insights and diagnostic approach

The congenital dyserythropoietic anemias (CDAs) are a group of rare hereditary disorders characterized by congenital anemia, ineffective erythropoiesis with distinct morphologic features in bone marrow (BM) late erythroblasts, and the development of secondary hemochromatosis. Patients usually present with anemia, jaundice, splenomegaly, and suboptimal reticulocyte response for the degree of anemia. Aniso-poikilocytosis and basophilic stippling are commonly observed in the peripheral blood smear. The working classification initially proposed by Heimpel and Wendt is still used in clinical practice (CDA I, II, and III; Table 1). However, there are families that fulfill the general definition of the CDAs but do not conform to any of the 3 classical types (CDA variants, Table 1). The genes mutated in the majority of patients with CDA I and II have been previously described, whereas the CDA III gene was only recently identified. Additional genetic defects have been described in CDA variants. Because of these advancements, the diagnosis can now be confirmed by molecular testing in an increasing number of patients. The aim of this review is to update the molecular basis of this group of disorders and to outline the current diagnostic approach.