The spectrum of HPRT deficiency: an update.

Abstract

Since the discovery that a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) was responsible for the Lesch-Nyhan syndrome (1, 2), a number of HPRT-deficient patients with greatly varying phenotypes have been reported. These have included patients with the classic Lesch-Nyhan syndrome, those with the neurological manifestations and normal intelligence, and those with uric acid overproduction and its consequences as their only clinical symptoms. In 1981 we reported that an inverse correlation exists between HPRT activity and the severity of the accompanying symptoms, if the enzyme activity is measured in intact cells (3). We have now studied many more patients by this method and have a better idea of the degree of enzyme deficiency at which the various symptoms appear. In the course of these studies, two new phenotypes of HPRT deficiency have been identified, and in each case the degree of HPRT deficiency found in these patients appears to be appropriate for the respective phenotype.