Delineation of the motor disorder of Lesch–Nyhan disease

Abstract

Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia.

Recent Advances in the Molecular Pathogenesis of Dystonia-Plus Syndromes and Heredodegenerative Dystonias

“…Affected individuals typically suffer from hyperuricaemia, nephrolithiasis, gout or subcutaneous deposits of tophi [52]. Neurologically, all patients have severe motor dysfunction that is dominated by dystonia, with additional pyramidal features (spasticity, hyperreflexia and clonus) [54]. Self-injurious behaviour, including biting and head banging is common often accompanied by self-mutilation, impulsivity, striking or spitting at others, or use of socially unacceptable language [55-57].…”

Congenital insensitivity to pain and anhydrosis due to a rare mutation and that is complicated by inflammatory bowel disease and amyloidosis: a case report

“…Lesch–Nyhan syndrome is a rare genetic disorder characterized by the overproduction of uric acid, neurologic disability dominated by intellectual disability, dystonia, spasticity, and behavioral problems 7. Other clinical findings consistent with CIPA in this patient included insensitivity to pain, learning disabilities, seizures, joint dislocation, skin ulcers, and chronic osteomyelitis 3, 8, 9.…”

New Mutation Affecting Hypoxanthine Phosphoribosyltransferase Responsible for Severe Tophaceous Gout

“…Different HPRT1 mutations induce various levels of residual HPRT enzymatic activity, resulting in clinical symptoms of various severity 2 . Complete HPRT deficiency leads to the classic clinical phenotype of Lesch-Nyhan disease (LND), characterized by uric acid overproduction and its sequelae (nephrolithiasis, gout, and tophi), motor dysfunction, and behavioral problems including recurrent self-injury 3 .…”