A-thalassemia with one defective gene.

• A. Silent carrier
• B. Thalassemia minor
• C. Thalassemia major
• D. Thalassemia intermedia

Answer: (A)

A single alpha-globin gene deletion leaves three functional alpha-globin genes, which is enough to maintain normal hemoglobin production. Clinically, this results in a silent carrier state: the person typically has no symptoms and normal hematologic studies, though mild microcytosis can sometimes be present. If two alpha genes are deleted, you get thalassemia trait with mild anemia and microcytosis. Three deletions (HbH disease) can cause moderate to significant anemia, and four deletions lead to hydrops fetalis with little to no viable life, due to almost complete lack of alpha-globin. So one defective gene best fits the silent carrier description.