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.


TERMINOLOGY


Abbreviations



  • Congenital dyserythropoietic anemia (CDA) I-III


Synonyms



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


Definitions



  • 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


ETIOLOGY/PATHOGENESIS


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


Pathogenesis



  • Ineffective erythropoiesis


  • Increased erythroid lineage in bone marrow with inadequate erythrocyte production


  • Reduced reticulocyte count for degree of anemia


Incidence/Ethnicity



  • 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


CLINICAL ISSUES


Presentation



  • 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


Treatment



  • 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)


Prognosis



  • Generally excellent


  • Iron overload adverse impact


IMAGE FINDINGS


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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