Pyruvate kinase (PK) deficiency (OMIM #266200) is caused by mutations in the PKLR gene that encodes PK (chromosome 1q21). This disorder is the most common erythrocyte enzyme defect that causes hereditary non-spherocytic hemolytic anemia. It is transmitted as an autosomal recessive trait. On the basis of gene frequency, it was estimated that the prevalence of homozygous PK deficiency is 51 cases per million in the US white population. Based on data in a health registry, it was estimated that the prevalence of PK deficiency in northern England is 3.3 per million. PK deficiency has a worldwide distribution, but may be more common among individuals of northern European descent. Herein, the pathophysiology of PK deficiency is discussed. The clinical manifestations of this disorder are reviewed with emphasis on the complication of iron overload.

Etiology and pathogenesis

Mature erythrocytes depend on the glycolytic production of adenosine triphosphate (ATP) to meet metabolic requirements. Deficiencies in several glycolytic enzymes can result in hemolytic anemia. These types of hemolytic anemia are not associated with a distinctive morphologic abnormality of erythrocytes, and thus are known collectively as congenital non-spherocytic hemolytic anemias. Most of these disorders are rare and are transmitted as autosomal recessive disorders.

PK deficiency is the most common erythrocyte glycolytic enzymopathy. The predominant PK isoenzyme present in erythrocytes is the R form, encoded by PKLR. Multiple mutations can lead to PK deficiency, and the type of mutation may determine in part the severity of the clinical phenotype.