Nejm 1976;295:710

Cause:Genetic

Pathophys:Impaired -Hgb chain synthesis, absolute or qualitative, and often associated with mental retardation (gene linkage) or fetal hydrops (Nejm 1981;305:607, 638). Thus homozygote unable to make Hgb A ( ₂ß₂), Hgb A2 ( _{2 2}), or Hgb F ( _{2 2}).

Increased prevalence in Asians, Shiite Arabs (Nejm 1980;303:1383), and all populations exposed to malaria because of heterozygous individuals have some resistance

Sx:

Homozygotes: severe disease at birth with hydrops fetalis, ie, anasarca due to anemia

Heterozygotes: none or mild anemia

Si:Homozygotes: splenomegaly, increased marrow proliferation and space

Homozygotes: perinatal death

Heterozygotes: severe disease when combined with another hemoglobin abnormality; hemosiderosis/iron overload

Lab:

Hem:In both homo- and heterozygotes, peripheral smear shows rbc stippling (rna and mitochondria), siderocytes, targets, "ghosts," and bizarre forms

In heterozygote, MCV <73 m³, Hgb A₂ <3.5%; iron levels normal (Nejm 1973;288:351); normal Hgb proportions, or Hgb H (ß₄) increased (r/o acquired Hgb H, rarely in erythroleukemics—Nejm 1971;285:1271)

In homozygote, Hgb electrophoresis shows no Hgb A, A₂, or F; Hgb Barts ( ₄) (Nejm 1990;323:179) and/or Hgb H may be present; both the latter are incompetent O₂ carriers

Rx:Transfusions, beware of iron overload