RESUMO
Astrocytes play crucial roles in maintaining brain homeostasis and in orchestrating neural development, all through tightly coordinated steps that cooperate to maintain the balance needed for normal development. Here, we review the alterations in astrocyte functions that contribute to a variety of developmental neurometabolic disorders and provide additional data on the predominant role of astrocyte dysfunction in the neurometabolic neurodegenerative disease glutaric acidemia type I. Finally, we describe some of the therapeutical approaches directed to neurometabolic diseases and discuss if astrocytes can be possible therapeutic targets for treating these disorders.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Astrócitos/patologia , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/terapia , Encéfalo/patologia , Glutaril-CoA Desidrogenase/deficiência , Doença de Alexander/diagnóstico , Doença de Alexander/metabolismo , Doença de Alexander/patologia , Doença de Alexander/terapia , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Antioxidantes/uso terapêutico , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encefalopatias Metabólicas/metabolismo , Encefalopatias Metabólicas/patologia , Ceruloplasmina/deficiência , Ceruloplasmina/metabolismo , Dieta/métodos , Gerenciamento Clínico , Glucose/uso terapêutico , Glutamato-Amônia Ligase/deficiência , Glutamato-Amônia Ligase/metabolismo , Glutaril-CoA Desidrogenase/metabolismo , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/metabolismo , Encefalopatia Hepática/patologia , Encefalopatia Hepática/terapia , Homeostase , Humanos , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/patologia , Distúrbios do Metabolismo do Ferro/terapia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/terapia , Neurogênese/efeitos dos fármacos , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/metabolismo , Doença de Niemann-Pick Tipo C/patologia , Doença de Niemann-Pick Tipo C/terapia , Doença da Deficiência de Piruvato Carboxilase/diagnóstico , Doença da Deficiência de Piruvato Carboxilase/metabolismo , Doença da Deficiência de Piruvato Carboxilase/patologia , Doença da Deficiência de Piruvato Carboxilase/terapia , Desintoxicação por SorçãoRESUMO
Alexander disease (AxD) is a rare neurodegenerative disorder related to mutations in the glial fibrillary acidic protein gene. We report the case of a child with disease onset at the age of 3 months and a novel mutation in the glial fibrillary acidic protein gene. Peculiar aspects were initially atypical clinical and magnetic resonance imaging (MRI) findings, which became typical during follow-up. The child was born after an uneventful pregnancy, presented initially only as a failure to thrive. The first MRI examination demonstrated obstructive hydrocephalus and cerebral white matter abnormalities (which were more prominent posteriorly). During follow-up, her clinical picture became typical of AxD with macrocephaly and neurodevelopmental delay. Sequential MRI examinations showed frontal white matter involvement, together with exuberant forniceal lesions and areas of contrast enhancement.