A newborn tests positive for G6PD deficiency. Which biochemical consequence best describes its effect on red blood cells under oxidative stress?

• A. Decreased NADPH production leading to reduced glutathione regeneration and hemolysis
• B. Increased NADPH production
• C. Increased glutathione regeneration
• D. Decreased pyruvate production

Answer: (A)

Red blood cells rely on the pentose phosphate pathway to generate NADPH, which is needed to keep glutathione in its reduced form. In G6PD deficiency, NADPH production is impaired. When oxidative stress hits, glutathione normally detoxifies reactive oxygen species by cycling between its reduced and oxidized forms, a process that requires NADPH to regenerate reduced glutathione. Without enough NADPH, glutathione cannot be replenished, ROS accumulate, and the red cell membrane becomes damaged, leading to hemolysis. So the best description is decreased NADPH production leading to reduced glutathione regeneration and hemolysis.