Congenital Dyserythropoietic Anemia

Congenital Dyserythropoietic Anemia

Kathryn Foucar, MD

Peripheral blood smear from a 60-year-old woman with CDA III shows anemia, macrocytosis, and mild anisopoikilocytosis. (Courtesy R. Brynes, MD.)

Peripheral blood smear from a 39-year-old woman with longstanding macrocytic anemia shows marked anisopoikilocytosis; blood and bone marrow are compatible with CDA II.



  • Congenital dyserythropoietic anemia (CDA) I-III


  • Hereditary erythroblast multinuclearity with positive acidified serum (HEMPAS) (for CDA II)


  • Hereditary erythrocyte maturation disorder

    • Variably severe anemia

    • Anisopoikilocytosis of red blood cells (RBC)

  • Distinctive morphologic abnormalities of erythroid lineage cells within bone marrow

    • Internuclear bridging

    • Multinucleation

    • Nuclear budding, karyorrhexis

  • 3 major subtypes


Genetic Features

  • Autosomal recessive or autosomal dominant inheritance

  • Genetic defect primarily involving mitosis

  • Genetic localization for CDA I, II, III described

    • CDAN1 mutation in CDA I results in abnormal codanin-1 protein


  • Ineffective erythropoiesis

  • Increased erythroid lineage in bone marrow with inadequate erythrocyte production

  • Reduced reticulocyte count for degree of anemia


  • Rare; generally limited to family kindreds or geographic regions

    • Italy, Sweden, Israeli Bedouins, Lebanon, India, Japan, China

  • Approximately 400 family kindreds in Europe

  • Some association with consanguinity for autosomal recessive types

  • Very rare sporadic cases



  • Age

    • Blood & bone marrow abnormalities present at birth

    • Age at disease presentation highly variable

      • May manifest at birth or early infancy

      • Manifestation may be as late as middle age

    • Most cases diagnosed by early adulthood

    • May be asymptomatic

  • Symptoms of chronic moderate to severe anemia

  • Some patients may be jaundiced

  • Splenomegaly with variable hepatomegaly by adulthood in CDA I, CDA II

  • Some patients have skeletal abnormalities

  • Rare patients present with dysmorphic features

Laboratory Tests

  • Reticulocyte count suboptimal for degree of anemia

  • LDH (lactic dehydrogenase) elevated

  • Indirect bilirubin elevated in CDA I, CDA II

  • Acidified serum test positive in CDA II

  • RBC agglutination by anti-i & anti-I positive in CDA II

    • Variable in CDA I and CDA III

  • SDS-PAGE (polyacrylamide gel electrophoresis)

    • Abnormal in CDA II and CDA III

  • Genetic testing for codanin mutations may be positive


  • Transfusions may be required during infancy/early childhood

  • Other patients require lifelong transfusions

    • May require chelation therapy for iron overload

  • Cholecystectomy may be required

  • Splenectomy may improve hematocrit

  • Interferon-α (CDA I)

  • Hematopoietic stem cell transplant (CDA I, CDA II)


  • Generally excellent

  • Iron overload adverse impact


Radiographic Findings

  • Skull and other bone lesions due to increased hematopoiesis

  • Mediastinal and paravertebral masses due to extramedullary hematopoiesis

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Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Congenital Dyserythropoietic Anemia
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