Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism
Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism
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DOI：
10.1093/ajcn/80.6.1611
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发表时间：
2004-12-01
影响因子：
7.1
通讯作者：
Neubrander, JA
中科院分区：
文献类型：
--
作者：
James, SJ;Cutler, P;Neubrander, JA
背景资料：自闭症是一种复杂的神经发育障碍，通常出现在儿童早期，被认为受到遗传和环境因素的影响。虽然蛋氨酸和同型半胱氨酸的代谢异常已与其他神经系统疾病，这些途径还没有被评估的人与autosit.Objective：本研究的目的是评估血浆中的代谢产物的浓度在蛋氨酸转甲基和转硫途径在儿童自闭症诊断。设计：蛋氨酸、S-腺苷蛋氨酸（SAM）的血浆浓度。在20名自闭症儿童和33名对照儿童中测定了S-腺苷同型半胱氨酸（SAH）、腺苷、同型半胱氨酸、胱硫醚、半胱氨酸、氧化型和还原型谷胱甘肽。在异常代谢特征的基础上，在自闭症儿童的一个子集中开始了亚叶酸、甜菜碱和甲钴胺的有针对性的营养干预试验。相对于对照儿童，自闭症儿童的甲硫氨酸、SAM、高半胱氨酸、胱硫醚、半胱氨酸和总谷胱甘肽的基线血浆浓度显着较低，而SAH、腺苷、和氧化型谷胱甘肽。这种代谢特征与自闭症儿童甲基化能力受损（SAM与SAH的比率显著降低）和氧化应激增加（还原型谷胱甘肽与氧化型谷胱甘肽的氧化还原比率显著降低）一致。干预试验是有效的正常化的代谢失衡的自闭症children.Conclusions：增加的脆弱性氧化应激和甲基化能力下降可能有助于自闭症的发展和临床表现。
Background: Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism.Objective: The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism. Design: Plasma concentrations of methionine, S-adenosylmethionine (SAM). S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children.Results: Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children.Conclusions: An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.