This is a group of inherited disorders characterized by quantitatively and qualitatively altered erythropoiesis resulting in usually mild-to-moderate anemia. Premature destruction of erythroblasts in the bone marrow reduces their numbers reaching maturity. In addition, there is peripheral destruction of these dysplastic erythroblasts. Three main types of congenital dyserythropoietic anemia (CDA I-III) and four other extremely rare types have been described.
For CDA III: Anemia with Multinucleated Erythroblasts; Hereditary Benign Erythroreticulosis.
Unknown. For CDA I, approximately 200 cases, and for CDA II more than 120 cases have been described. CDA III is the rarest of the three well-defined forms.
CDA I: Autosomal recessive. Most cases originate from Europe, and consanguinity is a known risk factor. The defect has been mapped to chromosome 15q15.2.
CDA II: Autosomal recessive, but the mutations have been mapped to chromosome 20p11.23. Consanguinity is present in a few families. Both sexes are equally affected.
CDA III: Most of the knowledge about this type of CDA derives from the Swedish Västerbotten family. Inheritance is autosomal dominant (although sporadic cases have been reported), and the genetic defect has been mapped to chromosome 15q21.
Based on the clinical findings, examination of peripheral blood smear and bone marrow biopsy, laboratory results (bilirubin, ferritin, transferrin, haptoglobin), and genealogic tree.
CDA I: Clinically, the spectrum ranges from mild to severe. In approximately half of the cases, the diagnosis is made in the neonatal period secondary to significant anemia. In the other half, the diagnosis is commonly made later in childhood or adolescence secondary to mild anemia with intermittent jaundice, splenomegaly, and sometimes hepatomegaly. The hemoglobin level typically stays at around 90 g/L (range 66-116 g/L), so transfusions are rarely required. Macrocytosis may be present, and the reticulocyte count is normal or low. The peripheral blood smear shows anisocytosis (elliptocytosis) and poikilocytosis with dacryocystitis. Serum concentration of bilirubin is elevated, while haptoglobin is decreased. Iron overload (even without transfusions) may result in hepatic cirrhosis and skin and endocrine changes. Biliary complications (eg, bile duct obstruction, pancreatitis, bile peritonitis) may lead to sepsis. Bone marrow aspirate reveals erythroid hyperplasia with significant nuclear dysplasia (irregular, karyorrhectic, binucleate, trinucleate appearance). Long chromatin strands surrounded by microtubules forming intercellular bridges and connecting the nuclei of two otherwise almost separated cells are considered typical for CDA I (although it may be seen in other forms of CDA). Erroneously, a β-thalassemia trait can be mimicked by increased percentage of hemoglobin A2 and the α-/non–α-globin chain synthesis ratio. Severe forms, usually occurring before or at birth with hemoglobin levels as low as 30 g/L requiring regular transfusions, have been described. Occasionally, the presenting features are dysmorphic body ...