Clinical Information

Deficiencies of most of the enzymes of the Embden-Meyerhof (glycolytic) pathway, including pyruvate kinase (PK), have been reported. PK deficiency (OMIM 266200) is the erythrocyte enzyme deficiency most frequently found to be a cause of chronic nonspherocytic hemolytic anemia. It is an autosomal recessive disorder, and parents of affected patients are typically carriers. Some PK carrier states can exacerbate other red blood cell disorders (ie, coincident glucose 6-phosphate dehydrogenase deficiency or hemoglobin S trait).

Clinically significant PK deficiency manifests in widely variable severity ranging from incidental compensated mild normocytic anemia to severe anemia. Neonatal jaundice is very common, and a significant subset of neonates have perinatal complications. Other symptoms include early gallstones and splenomegaly. Iron overload, even in the absence of frequent transfusions, is very common. Rare severe PK deficiency is associated with hydrops fetalis/fetal demise or unexplained noninfectious hepatic failure. Acquired PK deficiency can arise secondary to myeloid neoplasms.