4.3 Congenital dyserythropoetic anaemia (CDA)

CDA is, in fact, a heterogeneous group of defects of erythropoiesis with medullary abortion of the erythroblasts before maturing to reticulocytes (dyserythropoiesis), and important erythrocyte morphology abnormalities. Clinically, CDA is characterized by anaemia, usually macrocytic, and iron overload. To date, five clinical forms of CDA have been described: CDA I, CDA II, CDA III, CDA IV and CDA with thrombocytopenia [17]. The first two (CDA I and CDA II) have an autosomal recessive hereditary pattern and the other two (CDA III and CDA IV) are autosomal dominant. Thrombocytopenia with CDA has an inheritance linked to the X chromosome. The two best known CDAs are CDA I (OMIM 224120) characterized by a marked dyserythropoiesis and frequent inter nuclear chromatin bridges and CDA II (OMIM 224100), characterized by marked dyserythropoiesis associated with erythroblastic binuclearity or multinuclearity, and the presence of erythroblasts with double cell membrane (Figure 2). CDA III (OMIM 105600) is a ultra-rare disease where the marked dyserythropoiesis is associated with severe nuclear size and chromatin morphological abnormalities that resemble an erythroleukemia or Di-Guglielmo disease.

CDA I is due to mutations of the CDAN1 gene or less frequently to mutations of the C15ORF41 gene, In a small percentage of cases the mutation is unknown.

Figure 2.

Typical bone marrow picture of Congenital Dyserythropoietic Anaemia type II also known by hereditary erythroblastic multinuclearity with positive acidified serum lysis (HEMPAS) test.

In CDA II, the disease is due to mutations of the SEC23B gene and in CDA III, its most frequent gene mutation is the KIF23 gene.
