RESUMO
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.
Assuntos
Distonia/fisiopatologia , Síndrome de Lesch-Nyhan/fisiopatologia , Adolescente , Adulto , Encéfalo/patologia , Paralisia Cerebral/fisiopatologia , Criança , Pré-Escolar , Transtornos de Deglutição/genética , Transtornos de Deglutição/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Disartria/genética , Disartria/fisiopatologia , Distonia/genética , Feminino , Humanos , Síndrome de Lesch-Nyhan/tratamento farmacológico , Síndrome de Lesch-Nyhan/patologia , Masculino , Hipotonia Muscular/genética , Hipotonia Muscular/fisiopatologia , Fenótipo , Estudos Prospectivos , Tratos Piramidais/fisiopatologia , Índice de Gravidade de DoençaRESUMO
Reports describing the neurological features of Lesch-Nyhan disease (LND) vary widely, thereby implying the involvement of different neurological substrates. The movement abnormalities in 20 patients with LND were investigated. Dystonia was the most frequent and severe movement disorder. At rest, hypotonia was more frequent than hypertonia. These findings are compatible with basal ganglia dysfunction in LND.
Assuntos
Síndrome de Lesch-Nyhan/diagnóstico , Síndrome de Lesch-Nyhan/patologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neuromusculares/diagnóstico , Humanos , Hipotonia Muscular/diagnóstico , Doenças Neurodegenerativas/patologia , Doenças Neuromusculares/patologiaRESUMO
Lesch-Nyhan disease (LND) is a rare X-linked recessive genetic disorder associated with cognitive impairment, choreoathetosis, hyperuricemia, and the hallmark symptom of severe and involuntary self-mutilation. This study examines data gathered from a survey of 64 families in the USA and abroad regarding the self-injury of their family members who have LND. The individuals with LND ranged in age from 1 to 40 years (mean 16 years 7 months, SD 11 years 2 months) and, with the exception of one, were males. The most common initial mode of self-mutilation, and the most frequently cited past or current behavior, was biting of lips and/or fingers. Other behaviors, in order of frequency, included head banging, extension of arms when being wheeled through doorways, tipping of wheelchairs, eye-poking, fingers in wheelchair spokes, and rubbing behaviors. Hierarchical cluster analysis identified patterns of association among the types of self-mutilation. Modes of self-mutilation in which external surfaces (such as a wheelchair component) served as instruments of self-injury tended to co-occur, as did biting of lips and fingers.
