RESUMEN
Leigh syndrome represents a complex inherited neurometabolic and neurodegenerative disorder associated with different clinical, genetic and neuroimaging findings in the context of bilateral symmetrical lesions involving the brainstem and basal ganglia. Heterogeneous neurological manifestations such as spasticity, cerebellar ataxia, dystonia, choreoathetosis and parkinsonism are associated with multisystemic and ophthalmological abnormalities due to >75 different monogenic causes. Here, we describe the clinical and genetic features of a Brazilian cohort of patients with Leigh Syndrome in which muscle biopsy analysis showed mitochondrial DNA defects and determine the utility of whole exome sequencing for a final genetic diagnostic in this cohort.
Asunto(s)
ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Secuenciación del Exoma , Enfermedad de Leigh/genética , Enfermedad de Leigh/metabolismo , Adolescente , Adulto , Anciano , Brasil , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Enfermedad de Leigh/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
The effect of agents commonly used in the therapy of mitochondrial complex I deficiency was examined in fibroblasts from a patient. Marked improvement was observed with riboflavin, which nearly normalized the adenosine triphosphate production. The study of adenosine triphosphate production rate in fibroblasts may improve decision-making in treatment design of patients with respiratory chain defects.
Asunto(s)
Adenosina Trifosfato/biosíntesis , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Enfermedad de Leigh/metabolismo , Fármacos Fotosensibilizantes/farmacología , Riboflavina/farmacología , Humanos , Técnicas In Vitro , Lactante , MasculinoRESUMEN
Localized water-suppressed 1H magnetic resonance spectroscopy was performed in an 11-month-old infant with Leigh syndrome. Spectra obtained from the basal ganglia, occipital cortex, and brainstem showed elevations in lactate, which were most pronounced in regions where abnormalities were seen with routine T2-weighted magnetic resonance imaging. This approach has allowed us to examine metabolism in brain tissue directly and noninvasively, and may provide a sensitive means for evaluating metabolic disease and the response to therapy in the brain.
Asunto(s)
Encéfalo/metabolismo , Lactatos/metabolismo , Enfermedad de Leigh/metabolismo , Encéfalo/patología , Femenino , Humanos , Hidrógeno , Lactante , Ácido Láctico , Enfermedad de Leigh/diagnóstico , Imagen por Resonancia Magnética , Espectroscopía de Resonancia MagnéticaRESUMEN
Leigh's disease is also known as subacute necrotizing encephalomyelopathy. The outstanding clinical features are alterations of the state consciousness, cranial nerve manifestations and bilateral pyramidal signs. The disease is a result of unexplained biochemical disturbances in the private metabolism. In this article we present the clinical characteristics, its course and the features in the nuclear magnetic resonance in a child with Leigh's disease.