Congenital Dyserythropoietic Anemias

 The congenital dyserythropoietic anemias (CDAs) are a group of relatively rare inherited anemias that share common features:

 Anemia:  mild to moderate (Hb = 8-11 g/dl).  Normocytic or macrocytic indicies are typical.

 Ineffective erythropoiesis:  The red cell half life is decreased to a variable extent in these disorders.  Granulopoiesis and thrombopoiesis are generally unremarkable

 Iron overload:  Increased plasma iron turnover.  Shortened half-life of plasma iron clearance.

 Multineucliar erythroid cells in B.M.

 Abnormalities of mature erythrocytes, including anisocytosis, poikilocytosis, and anisochromasia can be pronounced.  Reticulocytes are usually normal or slightly increased in number

 Three major types of CDA and a number of variants have been described.  The diagnosis and categorization of these disorders are facilitated by microscopic examination of the blood and bone marrow and by serologic testing.

 AR, Codanin-1  Manifests in early infancy, childhood & sometimes adolesance.  mild to moderate macrocytic anemia Hct 30%

 Mild hyperbillirubinemia.  Splenomegaly.

 Hypercellular erythroid marrow with megaloblastoid features: 1- v. Large cells containing an irregular nuclear mass with 2 segments. 2- Double nucleated cells. 3- Pairs of erythroblasts connected by a chromatin bridge.

 E.M: A- multiple nuclear membrane pores. B- uneven condensation of chromatin, leading to a “spongy” nuclear configuration (characteristic)

 HEMPAS (hereditary erythroblastic multinuclearity with positive acidified serum lysis test).  Most common type.

 AR, Defect in the surface membrane gluco- conjugated proteins (chrom. 20)  (N-acetyl-glucosaminyl-transferase II)  (alpha-mannosidase II)  Mean age of presentation 5y.

 Mild to severe anaemia (variable)  Splenomegaly & Jaundice are more prominent.  Iron overload is the most serious complication.  Hepatomegaly.

 +ve acidified serum test  Not to its own serum (+ve to ABO comp. Serum)  Succ. Lysis test –ve.  Anti-i and anti-I agglutinability +ve.

 AD, chrom 15  Usually asymptomatic.  Absent or minimal anemia.  N or minimal splenomegaly.

 Giant erythroblasts with upto 12 nuclei  E.M. Clefts in nuclei, autolytic areas in cytoplasm

 Anemia is often mild and requires no intervention.  Blood transfusion should be avoided unless necessary.  Splenectomy may be of benefit (CDA II).

 Patients should be routinely monitored for evidence of iron overload  Iron chelation therapy should be considered in the management of these patients after documentation of tissue iron overload.

 Identify family members.  Genetic counseling.