Snapshot A newborn baby with a history of hyperbilirubinemia at birth requiring phototherapy is noted to be jaundiced on day 12 of life. She is found to have elevated indirect bilirubinemia. Her LDH and haptoglobin are normal, though reticulocyte count is increased. A peripheral blood smear reveals no spherocytes. Phototherapy is started. Concerned about the timing of jaundice and lack of any morphologic abnormalities, the pediatrician orders a functional assay to investigate pyruvate kinase. Introduction Congenital intrinsic hemolytic anemia from RBC enzyme defect Genetics autosomal recessive Pathogenesis defective pyruvate kinase irreversible step in glycolysis (PEP → pyruvate) important in production of ATP recall RBCs only have glycolysis for energy production as they lack mitochondria ↓ ATP rigid RBCs → easily lysed RBCs Epidemiology most common cause of non-spherocytic inherited hemolytic anemia rare disorder Presentation Symptoms neonatal hemolytic anemia severity ranges from life-threatening to mild hemolysis pigmented gallstones Physical exam jaundice in a newborn hepatosplenomegaly Evaluation ↑ serum 2,3-BPG Extravascular hemolysis corrected reticulocytosis is ≥ 3% variable to ↓ haptoglobin variable to ↑ LDH ↑ indirect bilirubin Negative Coombs test Peripheral blood smear no spherocytes echinocytes (RBC with thorny projections) different from acanthyocytes Normal osmotic fragility test Diagnostic test functional assay of RBC pyruvate kinase activity Differential Diagnosis Hereditary spherocytosis Elliptocytosis G6PD deficiency Thalassemias Treatment Blood transfusions as needed Iron chelation therapy with iron overload Splenectomy for severe cases Supportive therapy with folate Prognosis, Prevention, and Complications Prognosis depends on the severity of hemolysis Complications if severe may see fetal hydrops hyperbilirubinemia requiring phototherapy