An X-linked inborn error of metabolism caused by a deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).
Characterised by hyperuricaemia and a typical neurobehavioural phenotype, including a hyperkinetic movement disorder dominated by dystonia, attentional deficits, and behavioural disturbances with self-injury.
Should be considered when delayed development is accompanied by a hyperkinetic movement disorder, including dystonia, particularly when routine brain MRI is normal.
Should be suspected if a delayed development is accompanied by self-injurious behaviour or evidence of excessive production of uric acid.
Diagnosis is based on HPRT enzyme activity, preferably measured in live cells such as cultured fibroblasts, and on molecular genetic techniques demonstrating the gene mutation. Results might provide predictive clues about ultimate disease severity.
Currently, no curative treatment is available. Supportive care includes muscle relaxants for the movement disorder, and physical restraints or teeth extraction to prevent self-injury.
Lesch-Nyhan disease (LND) is an X-linked inborn error of metabolism, caused by a mutation in the gene encoding the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).   The first description was in 1964, when 2 brothers originally diagnosed with cerebral palsy were later recognised as suffering from a previously undescribed inherited metabolic disease because of the familial occurrence and unusual clinical features.  HPRT deficiency causes overproduction of uric acid, which may lead to hyperuricaemia, nephrolithiasis, gouty arthritis, and subcutaneous tophi.  In addition, patients exhibit a distinctive neurobehavioural phenotype, characterised by dystonia, attentional deficits, and behavioural disturbances including self-injury, presumably attributable to dysfunction of the basal ganglia dopamine system.  Patients with a partial enzyme deficiency (Lesch-Nyhan variants [LNV]) display an incomplete phenotype: overproduction of uric acid with or without neurological dysfunction, and no self-injury.  
Department of Neurology
Radboud University Nijmegen Medical Center
JEV has received research grants from The Netherlands Organisation for Scientific Research (NWO) and the Dutch Brain Foundation to conduct scientific research relevant to this topic.
Departments of Neurology and Human Genetics
HAJ has served on the Scientific Advisory Boards for the Lesch-Nyhan Syndrome Children's Research Foundation in the US and for Lesch-Nyhan Action in France. He has received grant support from the NIH, the Lesch-Nyhan Syndrome Children's Research Foundation, and Psyadon Pharmaceuticals for research on Lesch-Nyhan disease.
Department of Neurology
The University of Maryland School of Medicine
SGR is co-author of a study referenced in this monograph.
Associate Professor (Doc)
Head of the DNA Laboratory
Department of Child Neurology
Second School of Medicine
and University Hospital Motol
PS declares that he has no competing interests.
Use of this content is subject to our disclaimer