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.