Foundations · Year 1 · from Foundations
Case 1: Pyruvate Kinase Deficiency (Hemolytic Anemia)
Clinical Image
Source: Wikipedia - Pyruvate kinase deficiency - CC BY-SA 3.0
Case Presentation
A 4-year-old boy of Northern European descent is referred for evaluation of chronic anemia and intermittent jaundice. His parents report he has been pale since infancy and occasionally becomes more yellow during viral illnesses. Physical examination reveals pallor, mild scleral icterus, and splenomegaly. Laboratory studies show hemoglobin 8.5 g/dL, reticulocyte count 18%, total bilirubin 4.2 mg/dL (indirect predominant), LDH 450 U/L, and haptoglobin <10 mg/dL (low), consistent with chronic hemolysis. Direct Coombs test is negative. Peripheral blood smear shows polychromasia, echinocytes (spiculated cells), and rare spherocytes. Hemoglobin electrophoresis is normal. An erythrocyte enzyme panel reveals markedly reduced pyruvate kinase activity at 15% of normal. Genetic testing confirms compound heterozygous mutations in the PKLR gene. He is managed with folic acid supplementation and close monitoring. His elevated 2,3-BPG levels (a consequence of glycolytic intermediate accumulation) actually help compensate for his anemia by right-shifting the oxygen-hemoglobin dissociation curve.
Key Learning Points
- Pyruvate kinase deficiency is the most common glycolytic enzyme defect causing hemolytic anemia; mature red blood cells depend entirely on glycolysis for ATP since they lack mitochondria
- Without adequate pyruvate kinase activity, RBCs cannot generate sufficient ATP to maintain membrane pumps and cellular integrity, leading to premature destruction (hemolysis)
- The accumulation of glycolytic intermediates upstream of the block leads to elevated 2,3-BPG, which paradoxically benefits patients by increasing oxygen delivery to tissues