The most common enzymopathy of red blood cells is which deficiency?

• A. Pyruvate kinase
• B. Sphingomyelinase
• C. Hexokinase
• D. G6PD

Answer: (D)

Red blood cells rely on specific metabolic pathways to stay healthy, especially the hexose monophosphate (pentose phosphate) pathway that supplies NADPH to keep glutathione in the reduced form and protect hemoglobin from oxidative damage. The deficiency that most commonly disrupts this protective mechanism is G6PD deficiency, which impairs the first step of the pentose phosphate pathway and lowers NADPH production.

With less NADPH, oxidative stress from infections, certain drugs (like some antibiotics and antimalarials), or fava beans can overwhelm the red cells. Hemoglobin oxidizes and forms Heinz bodies, the cells become brittle, and hemolysis occurs, sometimes in an episodic fashion. This is why patients may present with sudden anemia, jaundice, and dark urine after a trigger, and why blood smears can show bite cells and Heinz bodies. The condition is X-linked, so it tends to affect males more often, and is particularly common in populations from malaria-endemic regions due to historical selective advantage.

Other listed enzymes are either not as commonly defective in red blood cells or are associated with different diseases. For example, pyruvate kinase deficiency also causes hemolysis but is less common and usually presents more chronically due to ATP depletion; sphingomyelinase deficiency relates to a lysosomal storage disorder (Niemann-Pick) rather than a primary red cell enzymopathy; hexokinase deficiency is not a typical widespread RBC enzymopathy.