A newborn male presents with hemolytic anemia and neonatal jaundice. No Heinz bodies are seen on peripheral smear. Enzyme assay confirms pyruvate kinase deficiency. What is the direct metabolic consequence that leads to red cell hemolysis in this condition?

• A ATP depletion impairing Na+/K+-ATPase and causing osmotic lysis ✓
• B Excess NADH causing oxidative damage to hemoglobin
• C Accumulation of 2,3-bisphosphoglycerate destabilizing the red cell membrane
• D Increased glucose-6-phosphate shunted to sorbitol via aldose reductase

Explanation

Pyruvate kinase (PK) catalyzes the last ATP-generating step of glycolysis (PEP → pyruvate + ATP). Red cells are entirely dependent on glycolysis for ATP. PK deficiency halts this step, depleting ATP and preventing Na+/K+-ATPase function, causing sodium influx, water entry, and hemolysis. 2,3-BPG does accumulate upstream but the primary hemolytic mechanism is ATP depletion. Oxidative damage (Heinz bodies) characterizes G6PD deficiency, not PK deficiency.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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