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The congenital dyserythropoietic anemias are a heterogeneous group of uncommon disorders characterized by anemia, the presence of multinuclear erythroid precursors in the marrow, ineffective erythropoiesis, and iron overload. Only the erythroid series shows significant abnormalities, with rare exceptions. Patients have been classified as types I, II, and III, but some patients who appear to fit into the general category of congenital dyserythropoietic anemias do not fit into any of these three groups. Types I and II congenital dyserythropoietic anemias are inherited as autosomal recessive disorders, and type III disease is transmitted as a dominant disorder. Type I disease is caused by mutations of the CDAN1 gene. Codanin-1, the gene product, is a cell-cycle–regulated protein of currently unknown function. Type II congenital dyserythropoietic anemia is also known as hereditary erythroblastic multinuclearity with a positive acidified serum test, or by its acronym HEMPAS. Abnormal complex carbohydrates are present in patients with the type II disease. SEC23B (20p11.23–p12), encoding the SEC23B component of the COPII complex, is the causative gene in most patients. It engenders a vesicle trafficking defect between the endoplasmic reticulum and the trans-Golgi and, in turn, a glycosylation abnormality. Although type III disease is clinically milder than the other two forms of congenital dyserythropoietic anemia, it shows a tendency for retinal angioid streaks and myeloma in the long term. There is no specific treatment for these disorders. Management includes red cell transfusion, removal of excess body iron by chelation therapy or judicious phlebotomy, splenectomy, and marrow transplantation. Only in severe forms of type I congenital dyserythropoietic anemia does interferon-α decrease the transfusion needs.

Acronyms and Abbreviations

Acronyms and abbreviations used in this chapter include: CDAN1 gene, codanin-1; E2F1, transcription factor 1; GDF15, growth differentiation factor 15; HEMPAS, hereditary erythroblastic multinuclearity associated with a positive acidified serum test; HFE gene H63D, gene of common hemochromatosis mutation; SLC4A, gene encoding band 3; UGT1A1, bilirubin UDP-glucuronosyltransferase 1A1 gene.

The term congenital dyserythropoietic anemia, coined by Heimpel and Wendt,1 applies to a group of rare hereditary refractory anemias characterized by ineffective erythropoiesis, erythroid multinuclearity, and accumulation of tissue iron. Splenomegaly is common. Anemia is usually first noted in infancy or childhood. The life span of circulating erythrocytes is moderately reduced, and the dominant factor in pathogenesis is a large component of intramedullary cell death. Ineffective erythropoiesis results in an anemia of variable severity associated with a mild macrocytosis, a normal, or at most slightly elevated, absolute reticulocyte count, a moderate increase in unglycosylated (indirect) bilirubin, a low haptoglobin, and a gradual increase in ferritin level. Congenital dyserythropoietic anemias have been classified into three types, named types I, II, and III. In addition, a number of cases that do not fit clearly into any of these three categories have been described.

In 2008, the German, Italian, French, Spanish, Polish, and British registries, covering most European countries, were merged. Eighty-eight cases of type I, 341 cases ...

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