RT Book, Section A1 Iolascon, Achille A2 Kaushansky, Kenneth A2 Lichtman, Marshall A. A2 Prchal, Josef T. A2 Levi, Marcel M. A2 Press, Oliver W. A2 Burns, Linda J. A2 Caligiuri, Michael SR Print(0) ID 1121092050 T1 The Congenital Dyserythropoietic Anemias T2 Williams Hematology, 9e YR 2015 FD 2015 PB McGraw-Hill Education PP New York, NY SN 9780071833004 LK hemonc.mhmedical.com/content.aspx?aid=1121092050 RD 2024/03/29 AB SUMMARYThe congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of rare disorders characterized by anemia, the presence of erythroid hyperplasia with multinuclear erythroid precursors in the marrow, ineffective erythropoiesis and secondary iron overload.* Only the erythroid series shows significant abnormalities, with rare exceptions. Patients have been classified as types I, II, and III, but several patients appearing with these general characteristics do not fit into any of the three groups. CDA types I and II are inherited as autosomal recessive disorders, and type III disease is inherited as an autosomal 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. In codanin-negative cases, C15ORF41 mutations can cause type I CDA. Type II CDA is also known as hereditary erythroblastic multinuclearity with a positive acidified serum test, or by its acronym HEMPAS. The vast majority of CDA type II cases are caused by mutations of the SEC23B gene. This gene encodes the cytoplasmic COPII (coat protein) component SEC23B, which is involved in the secretory pathway of eukaryotic cells. CDA type III disease is rarer than the other two forms and its erythroid production failure is accompanied by a tendency for the development of retinal angioid streaks and of myeloma in the long term. It is caused by KIF23 mutations, a gene encoding mitotic kinesin-like protein 1, which plays a critical role in cytokinesis. 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 allogeneic hematopoietic stem cell transplantation. Only in severe forms of type I CDA does interferon-α decrease transfusion needs.