PEDBASE.org - The Pediatric Database - Detailed information of CONGENITAL DYSERYTHROPOIETIC ANEMIA

CONGENITAL DYSERYTHROPOIETIC ANEMIA

DEFINITION:

A group of disorders characterized by a congenital defect in erythropoiesis and reticulocytosis resulting in erythroblast multinuclearity and anemia.

EPIDEMIOLOGY:

incidence: ? (210 cases reported)
age of onset:
- infancy to adulthood
- mean age: 15 years (Types I and II), 22 years (Type III)
risk factors:
- familial - autosomal recessive (Types I and II)
  - autosomal dominant (Type III)
- sex - Type I - M > F (1.25:1)
  Type II - M = F
  
  Type III - M > F (1.9:1)

PATHOGENESIS:

1. Background

considered to be one of at least 3 disorders where there is a congenital deficiency in erythroid precursors
- other congenital cytopenias:
  - Diamond-Blackfan Syndrome
  - AASE Syndrome

2. Genetic Defect(s)

genetic defect(s) -> ineffective and morphologically abnormal erythropoiesis (dyserythropoiesis) -> block at the mature erythroblast level (normal proerythroblasts with erythroid hyperplasia) but abnormal mature erythroblasts (polychromatophilic and orthochromatic erythroblasts)

PATHOLOGY (Bone Marrow):

1. Type I

dissociation of nuclear and cytoplasmic maturation (i.e., immature nuclear maturation)
immature megaloblastoid nuclei
binucleated
internuclear chromatin bridges

2. Type II

bi- and multinucleated mature erythroblasts
double cytoplasmic membrane (excess rER)
karyorrhexis, pluripolar mitoses

3. Type III

multinucleated mature erythroblasts
gigantoblasts (up to 12 nuclei per erythroblast)

CLINICAL FEATURES:

1. Type I (15% of cases)

mild to moderate anemia
jaundice (+/- icterus), moderate splenomegaly

2. Type II (60-65% of cases)

mild to severe anemia
jaundice, hepatosplenomegaly (hepatomegaly)

3. Type III (20-25% of cases)

mild to moderate anemia
hepatosplenomegaly

4. Complications

gallstones (from hemolytic anemia)
hemosiderosis (from increased GI iron absorption due to marked erythroid hyperplasia)

INVESTIGATIONS:

1. Serum

1. Type I:

Hb: macrocytic (mean = 90 g/L), low reticulocytes (1-7%)
normal WBC and platelets
smear - anisocytosis, poikilocytes, punctate basophilia, helmet and tadpole cells, Cabot's rings
elevated bilirubin (indirect), LDH

2. Type II:

Hb: normocytic (mean = 65 g/L), low reticulocytes (4%)
smear - anisocytosis, poikilocytosis, tear drops, basophilic stippling
pathognomonic - Type II CDA RBC's are lysed by 30% of acidified sera from normal individuals (these RBC's have a specific HEMPAS antigen while normal sera contain an anti-HEMPAS IgM antibody)
presence of fetal membrane antigen i

3. Type III:

Hb: macrocytic (mean = 80 g/L), low reticulocytes (2-4%)
smear - anisocytosis, poikilocytosis, basophilic stippling

2. Bone Marrow

see "Pathology"

MANAGEMENT:

1. Supportive

PRBC transfusions, splenectomy (Type II)

2. Hemosiderosis

prophylactic phlebotomy
iron chelators

Pediatric Database - CONGENITAL DYSERYTHROPOIETIC ANEMIA

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