In alpha-thalassemia with three gene deletions, which abnormal hemoglobin forms tetramers that damage red blood cells?

In alpha-thalassemia with three gene deletions, which abnormal hemoglobin forms tetramers that damage red blood cells?

• A. HbA
• B. HbF
• C. Hb Bart's
• D. HbH

Answer: (D)

When alpha-globin production is reduced by three gene deletions, there aren’t enough alpha chains to pair with the beta chains. The excess beta chains form tetramers called hemoglobin H (beta4). These HbH tetramers are unstable, precipitate inside red blood cells, and damage the cell membrane, leading to hemolysis and a hemolytic anemia with features such as Heinz bodies and cellular fragility. Hb Bart’s tetramers (gamma4) appear when all four alpha genes are deleted, not with three deletions, and are associated with severe fetal/neonatal disease rather than the RBC damage pattern seen in HbH disease. HbA is the normal adult hemoglobin and is reduced when alpha chains are deficient, but it is not the abnormal tetramer responsible for the damage in this scenario.

When alpha-globin production is reduced by three gene deletions, there aren’t enough alpha chains to pair with the beta chains. The excess beta chains form tetramers called hemoglobin H (beta4). These HbH tetramers are unstable, precipitate inside red blood cells, and damage the cell membrane, leading to hemolysis and a hemolytic anemia with features such as Heinz bodies and cellular fragility.

Hb Bart’s tetramers (gamma4) appear when all four alpha genes are deleted, not with three deletions, and are associated with severe fetal/neonatal disease rather than the RBC damage pattern seen in HbH disease. HbA is the normal adult hemoglobin and is reduced when alpha chains are deficient, but it is not the abnormal tetramer responsible for the damage in this scenario.