RESUMO
α-Amino adipic semialdehyde (α-AASA) accumulates in body fluids from patients with pyridoxine-dependent epilepsy because of mutations in antiquitin (ALDH7A1) and serves as the biomarker for this condition. We have recently found that the urinary excretion of α-AASA was also increased in molybdenum cofactor and sulfite oxidase deficiencies. The seizures in pyridoxine-dependent epilepsy are caused by lowered cerebral levels of pyridoxal-5-phosphate (PLP), the bioactive form of pyridoxine (vitamin B(6)), which can be corrected by the supplementation of pyridoxine. The nonenzymatic trapping of PLP by the cyclic form of α-AASA is causative for the lowered cerebral PLP levels. We describe 2 siblings with clinically evident pyridoxine-responsive seizures associated with increased urinary excretion of α-AASA. Subsequent metabolic investigations revealed several metabolic abnormities, all indicative for molybdenum cofactor deficiency. Molecular investigations indeed revealed a known homozygous mutation in the MOCS2 gene. Based upon the clinically evident pyridoxine-responsive seizures in these 2 siblings, we recommend considering pyridoxine supplementation to patients affected with molybdenum cofactor or sulfite oxidase deficiencies.
Assuntos
Ácido 2-Aminoadípico/análogos & derivados , Aldeído Desidrogenase/genética , Consanguinidade , Epilepsia/diagnóstico , Epilepsia/genética , Erros Inatos do Metabolismo dos Metais/diagnóstico , Erros Inatos do Metabolismo dos Metais/genética , Ácido 2-Aminoadípico/urina , Encéfalo/metabolismo , Encéfalo/patologia , Pré-Escolar , Análise Mutacional de DNA , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/tratamento farmacológico , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/urina , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Eletroencefalografia/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Epilepsia/urina , Éxons/genética , Feminino , Triagem de Portadores Genéticos , Homozigoto , Humanos , Lactente , Recém-Nascido , Leucovorina/uso terapêutico , Masculino , Erros Inatos do Metabolismo dos Metais/tratamento farmacológico , Erros Inatos do Metabolismo dos Metais/urina , Molibdoferredoxina/genética , Molibdoferredoxina/urina , Exame Neurológico/efeitos dos fármacos , Fosfato de Piridoxal/deficiência , Fosfato de Piridoxal/metabolismo , Piridoxina/uso terapêutico , Análise de Sequência de DNA , Sulfurtransferases/genéticaRESUMO
Disorders of creatine synthesis or its transporter resulting in neurological impairment with mental retardation and epilepsy have only been recognized in recent years. To date, the epileptic disorder observed in creatine transporter deficiency (CRTR-D) has been described as a mild phenotype with infrequent seizures and favorable response to common antiepileptic drugs. We report on a 5 year-old boy with known speech delay who presented with severe and refractory epilepsy. After extensive investigations, metabolite analysis and brain 1H-MRS suggested CRTR-D, which was confirmed by the detection of a known pathogenic mutation in the SLC6A8 gene (c.1631C>T; p.Pro544Leu).