Congenital dyserythropoietic anemia type II: molecular basis and clinical aspects

Congenital dyserythropoietic anemia of type II (CDA II) is a rare disorder, usually present in childhood, with a clinical picture of chronic anemia of mild to moderate degree, splenomegaly and intermittent or persistent jaundice. It is transmitted by autosomal recessive inheritance and is characterized by the presence of a large number of multinucleate and binucleate erythroblasts in the bone marrow and typical morphological abnormalities of the membrane of circulating erythrocytes. SDS-PAGE of red blood cell membrane proteins shows a narrower aspect and a faster migration of band 3 (anion exchange transporter). This aspect is consistent with decreased glycosylation of this protein. The genetic mutations responsible for the glycosylation defect in CDA II have not yet been identified. Analysis of carbohydrate structures and biochemical data indicate that the activity of either GnT II or alpha-Man II is reduced in different families, suggesting that the disease is genetically heterogeneous. Molecular cloning of the GnT II and alpha-Man II DNA sequences has allowed direct investigation of the genetic mutations underlying the glycosylation defect in CDA II patients to begin.