RESUMEN
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.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/terapia , Astrocitos/patología , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/terapia , Encéfalo/patología , Glutaril-CoA Deshidrogenasa/deficiencia , Enfermedad de Alexander/diagnóstico , Enfermedad de Alexander/metabolismo , Enfermedad de Alexander/patología , Enfermedad de Alexander/terapia , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/patología , Antioxidantes/uso terapéutico , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encefalopatías Metabólicas/metabolismo , Encefalopatías Metabólicas/patología , Ceruloplasmina/deficiencia , Ceruloplasmina/metabolismo , Dieta/métodos , Manejo de la Enfermedad , Glucosa/uso terapéutico , Glutamato-Amoníaco Ligasa/deficiencia , Glutamato-Amoníaco Ligasa/metabolismo , Glutaril-CoA Deshidrogenasa/metabolismo , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/patología , Encefalopatía Hepática/terapia , Homeostasis , Humanos , Trastornos del Metabolismo del Hierro/diagnóstico , Trastornos del Metabolismo del Hierro/metabolismo , Trastornos del Metabolismo del Hierro/patología , Trastornos del Metabolismo del Hierro/terapia , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/terapia , Neurogénesis/efectos de los fármacos , Enfermedad de Niemann-Pick Tipo C/diagnóstico , Enfermedad de Niemann-Pick Tipo C/metabolismo , Enfermedad de Niemann-Pick Tipo C/patología , Enfermedad de Niemann-Pick Tipo C/terapia , Enfermedad por Deficiencia de Piruvato Carboxilasa/diagnóstico , Enfermedad por Deficiencia de Piruvato Carboxilasa/metabolismo , Enfermedad por Deficiencia de Piruvato Carboxilasa/patología , Enfermedad por Deficiencia de Piruvato Carboxilasa/terapia , Desintoxicación por SorciónRESUMEN
Two patients with biotin-responsive multiple carboxylase deficiency, both presenting with predominant lactic acidosis, are reported. One with disease of early neonatal onset had considerable acute neurologic and persistent dermatologic abnormalities. The other, with late juvenile-onset disease, had chronic neurologic abnormalities without dermatologic findings. Early-onset cases generally have been associated with holocarboxylase synthetase deficiency, whereas those of juvenile onset have been characterized as representing defects in intestinal biotin absorption. However, enzyme analyses of fibroblasts from both patients, grown in biotin-deficient medium, revealed markedly diminished activities of pyruvate, propionyl-CoA, and beta-methylcrotonyl-CoA carboxylases, and all three enzymes showed normal activities after growth in biotin-rich medium. Furthermore, lymphoblast enzyme analysis in the patient with disease of early onset had previously revealed a defect in holocarboxylase synthetase, and fibroblast complementation studies showed that both patients belong to the bio complementation group. These findings indicate that considerable clinical heterogeneity exists among patients with holocarboxylase synthetase deficiency, an observation which does not permit differentiation of the biochemical forms of multiple carboxylase deficiency on the basis of age at onset and clinical presentation.