Key Takeaways

Pyruvate kinase deficiency (PKD) is the most frequent enzyme abnormality of the glycolytic pathway causing hereditary non-spherocytic hemolytic anemia.

PKD results in 50% reduction in ATP generation in red blood cells, which in turn leads to their early demise in the circulation.

Symptoms are primarily related to anemia.

Diagnosis is suspected in a patient with non-immune hemolytic anemia in whom other causes have been ruled out and is confirmed using enzymatic activity assay with or without DNA sequencing.

Complications include those of hemolysis (development of pigment gallstones [even after splenectomy]), aplastic crisis), iron overload (heart failure, liver disease, hypogonadism, hypothyroidism, hyperpigmentation), and splenectomy (overwhelming infection, venous thromboembolism).

Supportive treatment includes folic acid supplements, red cell transfusion, splenectomy and iron chelation.

Disease modifying treatment includes PK activator (Mitapivat, AG-348) or rarely hematopoietic stem cell transplant.

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