Pyruvate kinase deficiency

Pyruvate kinase deficiency

Updated: 7/14/2024

© Jun Wang, MD, PhD

 

General features

  • Autosomal recessive
  • Second most common RBC enzyme disorder
  • Most common cause of chronic hemolytic anemia from an RBC enzyme deficiency

Etiology

  • Mutations in the PKLR gene (>250 pathogenic variants)

Pathogenesis


Clinical findings
  • Mild to severe normochromic and normocytic anemia
  • Reticulocytosis
  • Symmetrical growth delay and/or failure to thrive
  • Icteric sclera and hyperbilirubinemia
  • Mild to moderate splenomegaly
  • Upper-right-quadrant tenderness
  • Cholecystolithiasis: Usually after the first decade of life but possibly in childhood
  • Chronic leg ulcers (adults)  

Laboratory findings

  • Evidence of normochromic and normocytic anemia
  • Evidence of non-immune hemolysis

Diagnosis

  • Screening for decreased PK activity using lysed RBCs if suspicious
  • Diagnosis confirmed by molecular testing

Management

  • Depending on the age
  • Before birth: intrauterine transfusion if fetal hydrops due to severe anemia
  • Neonatal period: phototherapy or exchange transfusion for hyperbilirubinemia
  • Infancy through adulthood: if anemia is severe

o   RBC transfusions                   

o   Folic acid supplementation   

o   Splenectomy

o   Iron chelation

o   Hematopoietic stem cell transplant, gene therapy, or the small molecule Mitapivat

  • Genetic/reproductive counseling

 

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