Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study

Abstract

Clinical diagnosis and severity of autism spectrum disorders (ASD) are determined by trained clinicians based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. To identify novel candidate metabolites as potential biomarkers for ASD, the current study applied capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) for high-throughput profiling of metabolite levels in the plasma of 25 psychotropic-naïve adult males with high-functioning ASD and 28 age-matched typically-developed control subjects. Ten ASD participants and ten age-matched controls were assigned in the first exploration set, while 15 ASD participants and 18 controls were included in the second replication set. By CE-TOFMS analysis, a total of 143 metabolites were detected in the plasma of the first set. Of these, 17 metabolites showed significantly different relative areas between the ASD participants and the controls (p<0.05). Of the 17 metabolites, we consistently found that the ASD participants had significantly high plasma levels of arginine (p = 0.024) and taurine (p = 0.018), and significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls in the second sample set. Further confirmatory analysis using quantification of absolute metabolite concentrations supported the robustness of high arginine (p = 0.001) and low lactic acid (p = 0.003) in the combined sample (n = 53). The present study identified deviated plasma metabolite levels associated with oxidative stress and mitochondrial dysfunction in individuals with ASD.

Potential serum biomarkers from a metabolomics study of autism

“…Emond and colleagues, 27 using a gas chromatography-mass spectroscopy (GC-MS)-based approach in an analysis of urine samples, built a multivariate statistical model that captured global biochemical signatures of autistic individuals, which enabled them to be distinguished very well from healthy children. Kuwabara and colleagues, 28 using capillary electrophoresis time-of-flight mass spectroscopy (CE-TOF MS) for high-throughput profiling of metabolite levels in plasma, identified deviated levels of plasma metabolites associated with oxidative stress and mito chondrial dysfunction in individuals with ASD.…”

Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology

“…Arginine has been described to be higher in plasma samples of ASD children. 40 Excessive arginine is thought to induce oxidative stress via NO production. 41 We also found perturbations of guanidinosuccinic acid and methylguanidine, which are produced from oxidation of argininosuccinic acid and creatine, respectively, by free radicals.…”

Functional Characterization of 5-Oxoproline Transport via SLC16A1/MCT1

“…Grioli et al (6) reported that 5-oxoproline was effective in improving some verbal memory functions in subjects affected by age-related memory decline. A recent study has shown that 5-oxoproline could become a possible biomarker for autism spectrum disorders (7).…”