• Etiology: autosomal recessive defect of pyruvate kinase
• Pathophysiology
  • Glucose is the only energy source in RBCs
  • Pyruvate kinase catalyzes the last step of glycolysis (i.e., irreversibly converts phosphoenolpyruvate into pyruvate)
  • Absence of pyruvate kinase → ATP deficiency in RBC
  • ATP deficiency disrupts the cation gradient along the RBC membrane → rigid RBCs → ↑ hemolysis (extravascular)
  • Accumulation of 2,3-bisphosphoglycerate → ↑ release of O2 from Hb → masks symptoms of anemia
• Clinical symptoms
  • Seldom asymptomatic
  • Typically newborn jaundice due to hemolysis and history of exchange transfusions
  • Splenomegaly
  • Pallor, fatigue, weakness
  • In rare cases: hydrops fetalis
• Diagnosis
  • ↓ Pyruvate kinase enzyme activity
  • PKLR gene mutation
  • Blood smear: burr cells
• Therapy
  • Phototherapy and/or exchange transfusions
  • In the case of severe anemia or excessively enlarged spleen: splenectomy