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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