The term congenital dyserythropoietic anemia (CDA) encompasses a group of rare heritable disorders characterized by anemia, ineffective erythropoiesis, structural and functional abnormalities of erythroblasts and mature erythrocytes, and increased iron absorption. CDA type I is the second most prevalent subtype (OMIM #224120). CDA type II is the most common subtype (OMIM #224100). CDA type II is often described by the acronym HEMPAS (hereditary erythroblastic multinuclearity with positive acidifed serum test). The clinical manifestations of these two subtypes of CDA are reviewed herein with an emphasis on the complication of iron overload.

General characteristics

Characteristics shared by patients with various subtypes of CDA include ease of fatigue, pallor, scleral icterus, jaundice, and splenomegaly. Some patients have abnormal fingernails or toenails, abnormal shapes or size of bones in the feet, or scoliosis. Circulating erythrocytes are often macrocytic and may have abnormal expression of membrane antigens. The bone marrow typically reveals erythroid hyperplasia, CDA erythroblasts are often enlarged, and have abnormal nuclear contours, nuclear fragmentation (karyorrhexis), or multinuclearity. In some patients with CDA, the rate of erythrocyte destruction is increased, resulting in anemia, reticulocytosis, and hyperbilirubinemia.

Congenital dyserythropoietic anemia type I (OMIM #224120)

Clinical manifestations

The median age at diagnosis is about 17 years (range birth to about age 45 years). In a study of 70 Israeli Bedouin patients with CDA type I, 64% had identifiable abnormalities at birth.