In alpha-thalassemia, three genetic mutations are associated with which condition?

• A. Alpha-thalassemia major
• B. Chronic anaemia
• C. Alpha-thalassemia minor
• D. No symptoms

Answer: (B)

Mutations in alpha-thalassemia reflect how many alpha-globin genes are deleted. The more deletions, the more severe the problem with making alpha-globin. When three alpha-globin genes are deleted, the body produces HbH disease, a form of alpha-thalassemia. In HbH disease, unstable hemoglobin tetramers (HbH) form and damage red blood cells, leading to ongoing, chronic hemolysis and anemia. That’s why three mutations are associated with chronic anaemia.

For context: deleting one gene typically causes no symptoms (silent carrier), deleting two genes causes alpha-thalassemia trait/minor with mild anemia, and deleting all four genes causes alpha-thalassemia major (usually hydrops fetalis and often fatal).