Epidemiology
- Beta thalassemia: most commonly seen in people of Mediterranean descent
- Alpha thalassemia: most commonly seen in people of Asian and African descent
Mnemonic
Alpha thalassemia is common in Asia and Africa.
Etiology
Pathophysiology
- Inefficient erythropoiesis → anemia
- Beta-thalassemia minor and major: faulty β-globin chain synthesis → ↓ β-chains→ ↑ γ-,δ-chains → ↑ HbF and ↑ HbA2.
- Alpha-thalassemia intermedia (HbH disease) and alpha-thalassemia major (Bart’s disease): faulty α-globin chain synthesis → ↓ α-chains → impaired pairing of α-chains with β-chains and γ-chains→ ↑ free β-, γ-chains → ↑ HbH, ↑ Hb Barts
- Sickle cell anemia: Point mutation in the β-globin gene (chromosome 11) → glutamic acid replaced with valine (single amino acid substitution) → 2 α-globin and 2 mutated β-globin subunits create pathological hemoglobin S (HbS).
- Increased hemolysis: One of the chains (either α or β) is reduced → compensatory overproduction of other chains → excess globin chains precipitate and form inclusions within RBCs → erythrocyte instability with hemolysis
- Anemia → ↑ erythropoietin → bone marrow hyperplasia and skeletal deformities
Tip
Hemoglobin A2 is elevated in beta-thalassemia to compensate for beta-globin–chain underproduction, but results in microcytic red cells that are prone to hemolysis. Increased erythrocyte turnover results in a misleadingly low hemoglobin A1c level. In such cases, measurement of glycated serum proteins (ie, fructosamine) is sometimes used to estimate glycemic control. See Diabetes mellitus > Hyperglycemia tests
Clinical features
Diagnostics
- Hb-electrophoresis
Tip
α-thalassemia minima vs β-thalassemia minor:
- Both asymptomatic
- α-thalassemia minima is normal on electrophoresis, while β-thalassemia shows narrowed HbA band and widened HbA2 band