RESUMO
The hypoxanthine-guanine phosphoribosyltransferase deficiency is an inborn error of purine metabolism, linked to the X chromosome. The clinical phenotypes associated with HPRT deficiency varied according to the level of enzyme deficiency, with a large spectrum of neurologic features like self-injurious behaviour in patients with complete deficiency. We report a 20-year-old man who had asymmetric polyarthritis, tophi, hyperuricemia, nephrolithiasis and mild neurologic symptoms with undetectable levels of HPRT activity in lysed erythrocytes. The genetic study identified the c.143G>A mutation in exon 3, GAA CGT (CTT>GAA CAT CTT (48arg>his). The presence of gouty arthropathy and chronic hyperuricemia in a young patient with neurological symptoms, suggests HPRT deficiency for which it is necessary its enzyme and molecular determination.
Assuntos
Hipoxantina Fosforribosiltransferase/deficiência , Hipoxantina Fosforribosiltransferase/genética , Síndrome de Lesch-Nyhan/genética , Humanos , Síndrome de Lesch-Nyhan/diagnóstico , Síndrome de Lesch-Nyhan/tratamento farmacológico , Síndrome de Lesch-Nyhan/enzimologia , Masculino , Mutação , Adulto JovemRESUMO
We previously demonstrated that intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, inhibited Na+,K+-ATPase activity and induced oxidative stress in rat striatum. In the present study, we evaluated the action of vitamins E and C on the biochemical alteration induced by hypoxanthine administration on Na+,K+-ATPase, TBARS, TRAP, as well as on superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities in striatum of adult rats. Animals received pretreatment with vitamins E and C or saline during 7 days. Twelve hours after the last injection of vitamins or saline, animals were divided into two groups: (1) vehicle-injected group and (2) hypoxanthine-injected group. For all parameters investigated in this research, animals were sacrificed 30 min after drug infusion. Results showed that pretreatment with vitamins E and C prevented hypoxanthine-mediated effects on Na+,K+-ATPase, TBARS and antioxidant enzymes (SOD, CAT and GPx) activities; however the reduction on TRAP was not prevented by these vitamins. Although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins might serve as an adjuvant therapy in order to avoid progression of striatal damage in patients affected by Lesch-Nyhan disease.
Assuntos
Ácido Ascórbico/farmacologia , Corpo Estriado/efeitos dos fármacos , Hipoxantina/antagonistas & inibidores , Síndrome de Lesch-Nyhan/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Catalase/efeitos dos fármacos , Catalase/metabolismo , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Progressão da Doença , Radicais Livres/metabolismo , Hipoxantina/metabolismo , Hipoxantina/toxicidade , Síndrome de Lesch-Nyhan/metabolismo , Síndrome de Lesch-Nyhan/fisiopatologia , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Resultado do Tratamento , Vitamina E/metabolismo , Vitamina E/uso terapêuticoRESUMO
El síndrome de Lesch-Nyhan es una enfermedad genética ligada al cromosoma X, originada por un defecto en el gen que codifica la hipoxantia guanina fosforribosiltransferasa (HGPRT). Esta enzima participa en la recuperación de la guanina e hipoxantina. La deficiencia enzemática conlleva una acumulación exagerada del ácido úrico. La deficiencia total o casi total de la enzima, produce el síndrome de Lesch-Nyhan, el cual se caracteriza por hiperruricemia, hiperaciduria, coreoatetosis, hiperreflexia, retardo mental y autoagresividad. La deficiencia parcial de la enzima ocasiona artritis gotosa y nefrolitiasis sin daño neurológico.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Síndrome de Lesch-Nyhan/cirurgia , Síndrome de Lesch-Nyhan/classificação , Síndrome de Lesch-Nyhan/complicações , Síndrome de Lesch-Nyhan/diagnóstico , Síndrome de Lesch-Nyhan/epidemiologia , Síndrome de Lesch-Nyhan/etiologia , Síndrome de Lesch-Nyhan/fisiopatologia , Síndrome de Lesch-Nyhan/genética , Síndrome de Lesch-Nyhan/imunologia , Síndrome de Lesch-Nyhan/mortalidade , Síndrome de Lesch-Nyhan/patologia , Síndrome de Lesch-Nyhan/tratamento farmacológico , Síndrome de Lesch-Nyhan/sangue , Síndrome de Lesch-Nyhan/terapiaRESUMO
Se presenta la historia clinica de 3 hermanos que pertenecen a una familia campesina cuyo cuadro clinico empeso al ano y medio de edad. Todos tenian cierta posicion fetal, con espasticidad y atrofia musculares, movimientos coreoatetosicos, lesiones de autoagresion y retardo mental. Los examenes clinicos y algunos de laboratorio orientaron al diagnostico de Enfermedad de Lesch-Nyham. Se considera que este trastorno se debe a anomalias enzimaticas como la ausencia de Hipoxantina Guanina Fosforibosil Transferasa y otras no bien identificadas. Por razones comprensibles estos examenes no se practican en nuestro medio por lo que el diagnostico se hace mas por el aspecto clinico y la uricemia elevada.
Assuntos
Criança , Humanos , Síndrome de Lesch-Nyhan , Bolívia , Síndrome de Lesch-Nyhan/tratamento farmacológicoRESUMO
A case is reported with a syndrome characterized by mental retardation, choreoathetosis, high levels of uric acid and aggressive, selfmutilation behavior, diagnosed as Lesch-Nyhan's syndrome. The most important features are, its appearance confined only to males, the absence of abnormalities along the prenatal and newborn periods, as well as the progressive impairment in the clinical course of the patient. The presence of high blood levels of uric acid which was controlled with the administration of allopurinol, the anemia, treated with ferrous sulfate and the complete absence of the AGPRT enzyme, were the laboratory findings. The clinical, pathophysiological and biochemical aspects of the treatment were also reviewed, as well as the experiences and findings reported in other series. The authors stress the very low frequency of these cases, the importance of making the diagnosis and the exceptional and eccentricity of the features which are part of the syndrome, such as the bites.