Attenuated variants of Lesch-Nyhan disease

Abstract

Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency.

Bilateral Vesicoureteric Reflux may be a Rare Association in Lesch-Nyhan Syndrome: A Case Report

“…3 The condition is almost exclusively diagnosed in the paediatric population though new diagnosis has been documented in adults. 20 Benz CMK et al 21 described the self-destructive behaviour of patients with LNS usually starts between the ages of 1.5 to 2 years or shortly after the primary teeth eruption. The auto-aggressive behaviour is manifested as lips and tongue biting, scratching with the fingernails, head banging.…”

New Mutation Affecting Hypoxanthine Phosphoribosyltransferase Responsible for Severe Tophaceous Gout

“…Collectively, patients with attenuated phenotypes are designated Lesch-Nyhan variants (LNV) 4 . The mildest form of LNV includes only overproduction of uric acid and its associated problems.…”

“…The Journal of on May 12, 2018 -Published by www.jrheum.org Downloaded from Letter nephrolithiasis 4,5,6 . The gout resulting from HPRT deficiency is remarkable in its severity and its propensity to form tophi 5,6 .…”

Severe Respiratory Acidosis in Status Epilepticus as a Possible Etiology of Sudden Death in Lesch–Nyhan Disease: A Case Report and Review of the Literature

“…Patients develop nephrolithiasis, gouty arthritis, and neurological manifestations including dystonia, choreoathetosis, ballismus, and a behavioral disease that includes disinhibited behavior and severe, stereotyped self-injury. Epilepsy may occur in LND, with estimates ranging from 2-3% Jinnah et al 2010); however, other studies have found a risk of seizure up to 30%, although this may be due to misinterpretation of abnormal movements as seizure (de Gemmis et al 2010;Markowski-Leeman and Jinnah 2013). Seizures in LND usually begin in childhood, and are typically classified as generalized tonic-clonic .…”