Greenwood Genetic Center, 113 Gregor Mendel Circle, Greenwood, SC 29646, USA.
Mol Autism. 2013 Jun 3;4(1):16. doi: 10.1186/2040-2392-4-16.
Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions.
We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays.
Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients.
Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs.
自闭症谱系障碍（ASD）是相对常见的神经发育障碍，其生物学基础尚未完全确定。已有一些生化标志物与 ASD 相关，但这些疾病仍没有实验室检测方法。
我们使用 Biolog Phenotype MicroArrays 分析了 137 名神经发育障碍患者（包括有和无 ASD 的患者）和 78 名正常个体的淋巴母细胞系的代谢谱。
淋巴母细胞代谢谱分析显示，87 名具有 ASD 临床特征的患者与 78 名对照相比，当色氨酸为唯一能量来源时，NADH 的生成平均减少。这些结果与与综合征或非综合征自闭症相关的行为特征相关，独立于个体的遗传背景。在没有色氨酸的情况下，NADH 的生成水平在非 ASD 智力障碍、精神分裂症或除行为特征外与综合征自闭症有几个相似之处的患者的细胞系中未观察到。对先前的一个小基因表达研究的分析发现，在 10 名患者中，一些参与色氨酸代谢途径的基因水平异常。
色氨酸是一些重要化合物的前体，如 5-羟色胺、喹啉酸和犬尿氨酸，这些化合物参与神经发育和突触发生。此外，喹啉酸是 NAD+的结构前体，NAD+是线粒体中关键的能量载体。此外，色氨酸代谢途径的 5-羟色胺分支生成 NADH。最后，喹啉酸和犬尿氨酸的水平受免疫系统的活性强烈影响。因此，色氨酸代谢减少可能会改变大脑发育、神经免疫活性和线粒体功能。我们发现色氨酸代谢减少似乎为 ASD 提供了一个统一的生化基础，并可能为 ASD 的诊断检测方法的开发提供了一个初步步骤。
