Which type of alpha-thalassemia results from deletion of three genes and produces a moderate hemolytic anemia?

• A. Hemoglobin H disease
• B. Hemoglobin Bart's
• C. Hydrops fetalis
• D. Thalassemia trait

Answer: (A)

In alpha-thalassemia, how many alpha-globin genes are deleted determines severity. Deleting three of the four alpha-globin genes leaves too little alpha chains to pair with the beta-like chains that are produced, so excess beta chains form unstable tetramers known as HbH (beta4). These HbH tetramers precipitate inside red blood cells, causing membrane damage and hemolysis, which leads to a moderate hemolytic anemia. Clinically you’d expect symptoms of anemia with signs like splenomegaly and elevated reticulocytes, and laboratory or smear findings may include target cells and HbH inclusions on special stains. This situation contrasts with four-gene deletions, which produce Hb Bart’s (gamma4) and hydrops fetalis, and with two-gene deletions, which cause a milder thalassemia trait. So, three gene deletions best fit Hemoglobin H disease.