Hemolytic anemia due to red cell pyruvate kinase deficiency

Pyruvate kinase deficiency (PKD) is the most common cause of hereditary non-spherocytic hemolytic anemia due to a red blood cell enzyme defect. It is caused by mutations in the PKLR gene, which encodes the red cell isoform of pyruvate kinase, a critical enzyme in the glycolytic pathway. When pyruvate kinase is deficient or dysfunctional, red blood cells cannot generate adequate adenosine triphosphate (ATP), leading to premature destruction of red blood cells (hemolysis). The condition is also known as pyruvate kinase deficiency of red cells, PK deficiency, or erythrocyte pyruvate kinase deficiency. The disease primarily affects the hematologic system. Clinical severity is highly variable, ranging from mild, well-compensated hemolytic anemia to severe, transfusion-dependent anemia presenting in the neonatal period. Key symptoms include chronic anemia, jaundice (due to elevated bilirubin from red cell breakdown), splenomegaly, and gallstones. Neonates may present with severe hyperbilirubinemia requiring exchange transfusion. Some patients develop iron overload over time, even without regular transfusions, due to chronic hemolysis and increased intestinal iron absorption. Aplastic crises triggered by parvovirus B19 infection can cause acute worsening of anemia. Management has traditionally been supportive, including red blood cell transfusions for severe anemia, folic acid supplementation, splenectomy (which can reduce but not eliminate hemolysis and transfusion requirements), and monitoring and treatment of iron overload with chelation therapy. In 2022, mitapivat (Pyrukynd), an oral activator of pyruvate kinase, was approved as the first disease-modifying therapy for adults with PKD, representing a significant advance in treatment. Hematopoietic stem cell transplantation has been performed in severe cases, and gene therapy approaches are under investigation.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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