Inherited deficiency of hypoxanthine-guanine phosphoribosyltransferase in X-linked uric aciduria (the Lesch-Nyhan syndrome and its variants).

Abstract

The amount of general interest in the inherited human X-linked neurological disease described by Lesch and Nyhan in 1964192 in two brothers with choreoathetosis, spasticity, mental retardation, compulsive self-mutilation (Figs. 1 and 2), and a markedly excessive production of uric acid seems far greater than the clinical prevalence of the disease would warrant. However, the basis for this interest is not difficult to understand. Once the abnormal gene product was identified as a gross deficiency in activity of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT),301 detailed study of this “experiment of nature” yielded insight into the operation of many genetic, biological, biochemical, physiological, and pathological processes that could be obtained in no other way. As with other such inborn errors of metabolism, the perturbation created by the abnormal gene product provided precise information on the role of the gene products not only at the primary level of enzyme activity but also at secondary and tertiary levels of cellular function. Description of the substantial amount of progress that has been made in elucidating the biochemical mechanisms responsible for some of the disturbances of function comprises a portion of this review.KeywordsUric AcidMutant EnzymePurine MetabolismPurine NucleotidePurine SynthesisThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.