Behavioral aspects of Lesch–Nyhan disease and its variants

Abstract

Self-injury is a defining feature of lesch-nyhan disease (LND) but does not occur in the less severely affected Lesch-Nyhan variants (LNV). The aim of this study was to quantify behavioral and emotional abnormalities in LND and LNV. Thirty-nine informants rated 22 patients with LND (21 males, 1 female), 11 males with LNV, and 11 healthy controls (HC; 10 males, 1 female) using two well-validated rating scales. The age of patients with LND ranged from 12 years 7 months to 38 years 3 months (mean 22 y 11 mo; sd 7 y 8 mo), whereas the age range of those with LNV was 12 years 9 months to 65 years (mean 30 y 7 mo; sd 15 y 2 mo), and the healthy controls were aged 12 years 4 months to 31 years 3 months (mean 17 y 10 mo; sd 5 y 7 mo). Behavioral ratings were based on the Child Behavior Checklist and the American Association On Mental Retardation's Adaptive Behavior Scale--Residential And Community, 2nd edition. Statistical analyses revealed that patients with LND showed severe self-injury together with problematic aggression, anxious-depressed symptoms, distractibility, motor stereotypes, and disturbing interpersonal behaviors. Patients with LNV were rated as being intermediate between the HC and LND groups on all behavior scales. Although the LNV group did not differ from hcs on most scales, their reported attention problems were as severe as those found in LND. We conclude that self-injurious and aggressive behaviors are nearly universal and that other behavioral abnormalities are common in LND. Although patients with LNV typically do not self-injure or display severe aggression, attention problems are common and a few patients demonstrate other behavioral anomalies.

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

“…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]. Most have cognitive decline [58,59] with significant reduction in global IQ, compounded by inattention.…”

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

“…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).…”

Lesch-Nyhan disease: from mechanism to model and back again

“…Most also have cognitive disability, although limitations are often not severe (Schretlen et al, 2001). Patients also show an unusual tendency towards difficult behaviors that include recurrent self-injury, with self-biting being particularly prominent (Schretlen et al, 2005;Preston, 2007). They may also exhibit other difficult behaviors such as impulsive acts of aggression, spitting, or use of foul or sexually charged language.…”