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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 the number of them reaching maturity. In addition, there is peripheral destruction of these dysplastic erythroblasts. Three main types of congenital dyserythropoietic anemia (CDA; types I, II, and III) and four other extremely rare types have been described.

For CDA III: Anemia with Multinucleated Erythroblasts; Hereditary Benign Erythroreticulosis.

CDA I: Almost 200 cases of this autosomal recessive inherited disorder have been described. Most cases originate from Europe, and consanguinity is a known risk factor. The defect has been mapped to 15q15.1-q15.3.

CDA II: More than 120 cases have been reported. Inheritance is also autosomal recessive, but the mutations have been mapped to 20q11.2. Consanguinity is present in a few families. Both sexes are equally affected.

CDA III: The rarest of the three well-defined forms of CDA. 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 15q21-q25.

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/liter (range 66-116 g/liter), 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 dacryocytosis. 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 (e.g., bile duct obstruction, pancreatitis, bile peritonitis) may lead to sepsis. Bone marrow aspirate reveals erythroid hyperplasia with significantly dysplastic nuclei (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/liter requiring regular transfusions, have been described. Occasionally, the presenting features are dysmorphic body signs rather than anemia related and may include short stature, platyspondyly, hypoplastic ribs, hearing loss, hypertelorism, micrognathia, large mouth, thick lips, large ears, syndactyly, aplasia/hypoplasia of distal phalanges, onychodysplasia, and brown skin patches. These patients may be on ...

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