Lesch-Nyhan syndrome: biochemical characterization of a case with attenuated behavioral manifestation

The activity and kinetic properties of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) were studied in fibroblasts from a Lesch-Nyhan syndrome (LNS) variant, with complete HGPRT deficiency in hemolysates, but with attenuated behavioral manifestation of the syndrome. The mutant HGPRT exhibited a 100-fold increase in Km for substrate phosphoribosyl-pyrophosphate, manifest in markedly decreased enzyme activity, being 2.5% of normal in cell extracts and about 0.6% of normal in intact cells. This degree of residual activity of the mutant enzyme is within the range found in patients with classical LNS.