Congenital dyserythropoietic anemias.

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Key words Name of the disease and synonyms Definition/diagnostic criteria Etiology Biological methods of diagnosis Incidence Management and treatments Unresolved questions and comments References Abstract Congenital dyserythropoietic anemias (CDA) result from diverse erythropoietic disorders; they lead to the defective production of red blood cells (RBC) and often mild hemolysis that attests to a qualitative defect of these RBC released into the circulation. Three forms of CDA have been characterized: types I, II and III. The shared symptoms include anemia of variable severity, intermittent jaundice, splenomegaly and hepatomegaly. Iron overload is progressive in types I and II. CDA I is often associated with dysmorphisms, particularly affecting the digits. Diagnosis of a CDA relies on light and electron microscopy examinations of the erythroblasts in a bone-marrow biopsy, which will demonstrate the presence of chromatin bridges between erythroblast nuclei and a spongy 'Swiss cheese' appearance of the condensed chromatin in CDA I; binucleated cells and endoplasmic reticulum remnants are seen in CDA II. Electrophoresis of erythrocyte membrane proteins also provides a sure diagnosis. The protein 4.1 level is low in CDA I, further associated with an unusual appearance of band 3 and the presence of reticular endoplasmic proteins - calreticulin, glucose regulatory protein 78 and isomerase disulfide - in CDA II. According to available estimations, CDA I and II incidence do not exceed 1/100 000 births per year. These forms are transmitted by recessive inheritance. CDA III results from dominant inheritance and is extremely rare. The genes responsible for CDA I, II and III have been localized to chromosomes 15q15.1-15.3, 20q11.2 and 15q21-q25, respectively. The gene implicated in CDA I was recently identified but the type and function of its product, codanine-1, remains to be established. The treatment of these diseases is essentially symptomatic. However, interferon-alpha attenuates the anemia of CDA I. The proteins causing these diseases and the underlying molecular mechanisms are still unknown.