Thalassemias

↓ synthesis of α- or β-globin chains of Hb → ≠ subunits → destruction of RBCs and erythroid precursors; ∴ anemia from hemolysis and ineffective erythropoiesis

α-thalassemia: deletions in α-globin gene complex on chr. 16 (nl 4 α genes)

3 α → α-thal-2 trait = silent carrier; 2 α -thal-1 trait α -thal minor = mild anemia

1 α → HbH (β4) disease = severe anemia, hemolysis, and splenomegaly

0 α genes → Hb Barts (ɣ4) = intrauterine hypoxia and hydrops fetalis

β-thalassemia: mutations in β-globin gene on chr. 11 → absent or ↓ gene product

1 mutated β gene → thal minor (or trait) = mild anemia (no transfusions)

2 mutated β genes → thal intermedia (occasional transfusions) or thal major (= Cooley’s anemia; transfusion-dependent) depending on severity of mutations

Special clinical manifestations (in severe cases): chipmunk facies, pathologic fractures, hepatosplenomegaly (due to extramedullary hematopoiesis), high-output CHF, bilirubin gallstones, iron overload syndromes (from chronic transfusions)

Diagnosis: MCV < 70, normal Fe, MCV/RBC count <13, ± ↑ retics, basophilic stippling; Hb electrophoresis: ↑ HbA2 (α2δ2) in β-thal; normal pattern in α-thal trait

Treatment: folate; transfusions + deferoxamine, deferasirox (oral iron chelator); splenectomy if ≥ 50% ↑ in transfusions; consider allogeneic HSCT in children w/ severe β-thal major