Progress in pathogenesis of glutaric aciduria type Ⅰ / 国际儿科学杂志

ABSTRACT

Glutaric aciduria type Ⅰ is an autosomal recessive disorder resulting from glutaryl-CoA dehydrogenase(GCDH) deflciency.Untreated patients commonly present with severe striatal degeneration and extrapyramidal sequelae during encephalopathic crises.GCDH deficiency leads to accumulation of glutaric acid and 3-hydroxyglutaric acid in tissues and body fluids (especially in brain),which are neurotoxic.There is no correlation between residual enzyme activity caused by mutations in GCDH and phenotype.The pathogenesis of glutaric aciduria type Ⅰ is complicated.Previous studies have demonstrated that glutaric and 3-hydroxyglutaric acids are synthesized in central nervous system and trapped because of limiting transport across the blood-brain barrier.The studies on metabolite-mediated neurotoxicity mainly focus on excitotoxicity,impairment of energy metabolism and oxidative stress.In addition,activation of astrocyte,vascular derangements,inflammatory processes may be a synergism of neurotoxicity.