A thalassemia with increased production of B-globin tetramers that damage RBCs.

A thalassemia with increased production of B-globin tetramers that damage RBCs.

• A. One defective gene
• B. Three defective genes
• C. Two defective genes
• D. Four defective genes

Answer: (B)

When the balance of globin production is off, the cell’s approach to making hemoglobin creates toxic byproducts. In alpha-thalassemia, alpha-globin production drops because most of the alpha-globin genes are deleted. The remaining beta (and other non-silent) chains then accumulate and form beta-globin tetramers. These HbH tetramers are unstable and precipitate inside red blood cells, causing damage, hemolysis, and anemia. This pattern—severe alpha-globin reduction with beta tetramer formation—is classic for HbH disease, the scenario described by the question. In milder cases, fewer alpha-globin genes are affected, producing milder symptoms, while complete loss of alpha-globin genes leads to hydrops fetalis with gamma-tetramers.

When the balance of globin production is off, the cell’s approach to making hemoglobin creates toxic byproducts. In alpha-thalassemia, alpha-globin production drops because most of the alpha-globin genes are deleted. The remaining beta (and other non-silent) chains then accumulate and form beta-globin tetramers. These HbH tetramers are unstable and precipitate inside red blood cells, causing damage, hemolysis, and anemia. This pattern—severe alpha-globin reduction with beta tetramer formation—is classic for HbH disease, the scenario described by the question. In milder cases, fewer alpha-globin genes are affected, producing milder symptoms, while complete loss of alpha-globin genes leads to hydrops fetalis with gamma-tetramers.