Red cell pyruvate kinase deficiency: from genetics to clinical manifestations

Pyruvate kinase deficiency is the most frequent enzyme abnormality of the E mbden-Meyerhof pathway causing hereditary non-spherocytic haemolytic anaemi a. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life-threatening neonatal anaemia and jaundice necess itating exchange transfusions. Splenectomy should be reserved for young pat ients who require regular blood transfusions. The gene encoding for pyruvat e kinase (PK-LR) has been localized to the long arm of chromosome I; the cD NA of R-type is 2060 bp long and codes for 574 amino acids. More than 130 d ifferent mutations, mostly missense, have so far been described in associat ion with PK deficiency, 1529A and 1456T being considered to be the most com mon mutations in Caucasians. Analysis of the three-dimensional structure of the enzyme may help in predicting the severity of the molecular defect. Fu rther data on clinical features of homozygous patients are needed, at least for some mutations, to allow a more precise genotype/phenotype correlation .