RT Book, Section A1 Iolascon, Achille A1 Russo, Roberta A1 Khoriaty, Rami A2 Prchal, Josef T. A2 Lichtman, Marshall A. SR Print(0) ID 1184011398 T1 The Hereditary Dyserythropoietic Anemias T2 Williams Hematology The Red Cell and Its Diseases YR 2022 FD 2022 PB McGraw Hill PP New York, NY SN 9781264269075 LK hemonc.mhmedical.com/content.aspx?aid=1184011398 RD 2024/03/29 AB SUMMARYThe hereditary dyserythropoietic anemias also known as congenital dyserythropoietic anemias (CDAs) are a group of hereditary disorders characterized by (1) anemia caused by ineffective erythropoiesis, (2) erythroid hyperplasia with increased percentage of bi/multinucleated erythroid precursors in the marrow, and often (3) hemochromatosis resulting from increased absorption of iron. The CDAs are classically divided into three types (CDA I, II, and III). CDA I is an autosomal recessive disease resulting from mutations in either CDAN1 or CDIN1 and is characterized by a “Swiss cheese” appearance of heterochromatin and internuclear chromatin bridges. CDA II, also an autosomal recessive disease, is the most common CDA type and results from mutations in SEC23B. CDA II is characterized by a double-membrane appearance of the red blood cell (RBC) plasma membrane, faster mobility of the RBC membrane protein band 3 by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE), and lysis of erythrocytes in a subset of acidified human sera, hence its prior designation as hereditary erythroblastic multinuclearity with a positive acidified serum test (commonly known as HEMPAS). CDA III is an autosomal dominant disease resulting from mutations in KIF23. CDA III is characterized by giant multinucleated erythroblasts and increased risk of development of angioid streaks and myeloma. Additional CDA variants resulting from mutations in KLF1, GATA1, ALAS2, LPIN2, CAD, COX4I2, and MVK have been reported. The CDA disease severity is highly variable, ranging from hydrops fetalis to minimal or no anemia. Treatment is largely individualized and depends on the severity of the disease and the specific clinical manifestation. Although allogeneic stem cell transplantation is the only curative modality, it can be justified in only a small subset of patients because of risks associated with the procedure. Other treatment modalities include RBC transfusion support, iron chelation, splenectomy, and interferon-α (for CDA I patients only).