Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome

Abstract

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency.

Purinergic signaling in human pluripotent stem cells is regulated by the housekeeping gene encoding hypoxanthine guanine phosphoribosyltransferase

“…The enzyme HPRT plays a major role in salvage purine biosynthesis by catalyzing the conversion of hypoxanthine and guanine to the nucleotides inosine monophosphate (IMP) and guanosine monophosphate (1,2). HPRT deficiency leads to the hallmark biochemical defect in LND: greatly increased de novo purine synthesis, with resulting elevated levels of oxypurines and tissue accumulation of uric acid, gout, and life-threatening nephrolithiasis (3,4). Although treatment with the xanthine oxidase inhibitor allopurinol effectively prevents hyperuricemia and renal damage in LND and thereby markedly extends the lifespan of patients, neither allopurinol nor any other treatment produces lasting improvement in neurological manifestations (5,6).…”

Gouty Synovitis of the Knee with Partial Hypoxanthine-guanine Phosphoribosyl Transferase Deficiency (Kelley-Seegmiller Syndrome): A Case Report

“…A case of complete HPRT deficiency, also known as Lesch-Nyhan syndrome, is characterized by hyperuricemia related disorders, such as acute arthritis, tophi, nephrolithiasis or even renal failure, with neurological manifestations including severe action dystonia, choreoathetosis, various degrees of mental retardation and self-mutilation 1) . In the case of partial HPRT deficiency, also called Kelley-Seegmiller syndrome, hyperuricemia-related disorders with a broad spectrum of neurological manifestations depending upon the degree of HPRT activity are apparent 2,3) . The present patient was already confirmed as having partial HPRT deficiency at 10 years of age by a pediatric physician in our hospital.…”

Metaphylaxis in Pediatric Urinary Stone Disease

“…HPRT deiciency, the severest form of which is Lesch-Nyhan syndrome, may occur with neurologic symptoms, mental retardation, and nephropathy, and in the early stages of life, kidney stones [74]. Deiciency of glucose-6-phosphate dehydrogenase leads to hyperuricemia, increasing the intracellular phosphoribosyl pyrophosphate in type 1 [75].…”