Defect in pyruvate kinase → ↓ ATP → rigid RBCs → extravascular hemolysis.- Autosomal recessive- In glycolysis, pyruvate kinase converts phosphoenolpyruvate into pyruvate irreversibly. This step is required in the degeneration of glucose into pyruvate to generate ATP (major anaerobic pathway). In the absence of pyruvate kinase, RBCs are deficient in ATP. This leads to a disturbed cation gradient among the RBC membrane, resulting in hemolysis.

Increases levels of 2,3-BPG → ↓ hemoglobin affinity for O₂.

Findings: - Hemolytic anemia in newborn- Splenomegaly, icterus, pallor, fatigue, weakness- In rare cases: lethal hydrops fetalis- Peripheral smear: Echinocytes