Congenital dyserythropoietic anemia (CDA) is an autosomal recessive disorder that affects erythropoiesis. Due to dyserythropoiesis (abnormal red blood cell production), erythroblasts (immature red blood cells) present in patients with CDA has an odd shape and extra nuclei that cannot develop into functional normal red blood cells. The clinical features of CDA include fatigue, weakness, pale skin, and further complications. CDA consists of three main forms: type I, type II, and type III. CDA type II varies between mild to severe and the majority of patients suffer from jaundice, hepatosplenomegaly, and gallstones. It is generally diagnosed throughout childhood or adolescence. The abnormal iron overload usually takes place following the age of 20 years, inducing complications comprising diabetes, heart disease, and cirrhosis. CDA type II is known to be the most common form of the disease, with over 300 reported cases.
Congenital dyserythropoietic anemia (CDA) type II is associated with mutations in the SEC23B (Sec23 homolog B) gene, which encodes a protein that regulates intracellular proteins transportation.
Zaki et al. (1989) reported two children with congenital dyserythropoietic anemia; one of them had Type I and the other Type II. Both were dependent on blood transfusion.
Amir et al. (2011) investigated the molecular basis of CDA II in 11 patients of North African (mainly Moroccan) Jewish descent. The patients came from 8 apparently unrelated families. The majority of patients (10/11) were homozygous for the common SEC23B mutation (E109K), with a relatively nonsevere phenotype. Haplotype analysis revealed a common genetic background in all patients. One patient was a compound heterozygote for the E109K mutation and a novel mutation, T710M. All patients were transfusion independent, with increasing iron overload with age. Amir et al. (2011) estimate the E109K mutation to be 2,400 years old.