Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation

Congenital dyserythropoietic anemia type I (CDA I) is a rare autosomal recessive disorder with ineffective erythropoiesis and iron overloading. More than 100 cases have been described, but with the exception of a report on a large Bedouin tribe, these reports include only small numbers of cases, and no data on the lifetime evolution of the disease are available. Since 1967, we have been able to follow 21 cases from 19 families for up to 37 years. Twenty-one patients with a confirmed diagnosis of CDA I exhibited chronic macrocytic anemia of variable severity, requiring regular red cell transfusions only in 2 individuals. Four developed gallstones before the age of 30 years. Fifteen of 16 cases alive at the time of analysis showed mutations of at least one allele from exons 6 to 28 within CDAN1. Iron overloading is to be expected in all patients. In 9 patients, iron depletion was started between the ages of 7 and 36 years. Splenectomy, which was performed in 7 patients, did not result in improvement of hemoglobin values. Five patients were treated with interferon α-2a, and all responded with a rise in hemoglobin concentration of between 25 and 35 g/L (2.5 and 3.5 g/dL) starting within 4 weeks.