Red cell pyruvate kinase deficiency: molecular and clinical aspects

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Abstract
Red cell pyruvate kinase (PK) deficiency is the most frequent enzyme abnormality of the glycolytic pathway causing hereditary non‐spherocytic haemolytic anaemia. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life‐threatening neonatal anaemia and jaundice necessitating exchange transfusions. Erythrocyte PK is synthesized under the control of the PK‐LR gene located on chromosome 1. To date, more than 150 different mutations in the PK‐LR gene have been associated with PK deficiency. First attempts to delineate the biochemical and clinical consequences of the molecular defect were mainly based on the observation of the few homozygous patients and on the analysis of the three‐dimensional structure of the enzyme. More recently, the comparison of the recombinant mutants of human red cell PK with the wild‐type enzyme has enabled the effects of amino acid replacements on the enzyme molecular properties to be determined and help to correlate genotype to clinical phenotype.