Which statement best describes the cause of G6PD deficiency-related hemolysis?

• A. Absence of decay-accelerating factor
• B. Antibody-mediated destruction of red cells
• C. Defective red cell membrane-tethering proteins
• D. Reduction in glutathione levels in red cells

Answer: (D)

G6PD deficiency causes hemolysis through impaired protection against oxidative stress in red blood cells. The enzyme normally drives NADPH production via the pentose phosphate pathway, and NADPH keeps glutathione in its reduced form. Reduced glutathione detoxifies reactive oxygen species; without it, oxidative damage accumulates in hemoglobin and the cell membrane, leading to hemolysis when the body encounters oxidants from certain drugs, infections, or foods like fava beans. Therefore, the key description is a reduction in glutathione levels in red cells, which explains why oxidative stress triggers hemolysis in this condition.

Other mechanisms described—absence of decay-accelerating factor (complement-mediated lysis), antibody-mediated destruction of red cells (autoimmune hemolysis), or defective red cell membrane-tethering proteins (membrane skeleton defects like hereditary spherocytosis)—do not account for the NADPH/glutathione–dependent vulnerability seen in G6PD deficiency.