Pyruvate kinase deficiency (PKD) is the most common cause of chronic hereditary non-spherocytic
hemolytic anemia and results in a broad spectrum of disease. The diagnosis of PKD requires a high index of suspicion and judicious use of laboratory tests that may not always be informative, including
pyruvate kinase enzyme assay and genetic analysis of the PKLR gene. A significant minority of patients with PKD have occult mutations in non-coding regions of PKLR which are missed on standard genetic tests. The biochemical consequences of PKD result in
hemolytic anemia due to red cell
pyruvate and
ATP deficiency while simultaneously causing increased red cell
2,3-diphosphoglycerate, which facilitates
oxygen unloading. This phenomenon, in addition to numerous other factors such as genetic background and differences in splenic function result in a poor correlation between symptoms and degree of
anemia from patient to patient. Red cell transfusions should, therefore, be symptom-directed and not based on a
hemoglobin threshold. Patients may experience specific complications, such as paravertebral extramedullary hematopoiesis and chronic debilitating
icterus, which require personalized treatment. The decision to perform
splenectomy or
hematopoietic stem cell transplantation is nuanced and depends on disease burden and long-term outlook given that targeted
therapeutics are in development. In recognition of the complicated nature of the disease and its management and the limitations of the PKD literature, an international working group of ten PKD experts convened to better define the disease burden and manifestations. This article summarizes the conclusions of this working group and is a guide for clinicians and investigators caring for patients with PKD.