Abstract
Background: Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-center study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms.Methods: One hundred and seventeen autistic children and 119 healthy children were recruited from research centers of 7 cities. Urine samples were assayed by 1H-NMR metabolomics analysis to detect metabolic variations. Multivariate statistical analysis, including principal component analysis (PCA), and orthogonal projection to latent structure discriminant analysis (OPLS-DA), as well as univariate analysis were used to assess differential metabolites between the ASD and control groups. The differential metabolites were further analyzed by receiver operating characteristics (ROC) curve analysis and metabolic pathways analysis.Results: Compared with the control group, the ASD group showed higher levels of glycine, guanidinoacetic acid, creatine, hydroxyphenylacetylglycine, phenylacetylglycine, and formate and lower levels of 3-aminoisobutanoic acid, alanine, taurine, creatinine, hypoxanthine, and N-methylnicotinamide. ROC curve showed relatively significant diagnostic values for hypoxanthine [area under the curve (AUC) = 0.657, 95% CI 0.588 to 0.726], creatinine (AUC = 0.639, 95% CI 0.569 to 0.709), creatine (AUC = 0.623, 95% CI 0.552 to 0.694), N-methylnicotinamide (AUC = 0.595, 95% CI 0.523 to 0.668), and guanidinoacetic acid (AUC = 0.574, 95% CI 0.501 to 0.647) in the ASD group. Combining the metabolites creatine, creatinine and hypoxanthine, the AUC of the ROC curve reached 0.720 (95% CI 0.659 to 0.777). Significantly altered metabolite pathways associated with differential metabolites were glycine, serine and threonine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism.Conclusions: Urinary amino acid metabolites were significantly altered in children with ASD. Amino acid metabolic pathways might play important roles in the pathogenic mechanisms of ASD.
Highlights
Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders characterized by social communication difficulties, narrow interests, and repetitive stereotyped behaviors [1]
The inclusion criteria for ASD group were: (a) children aged 2–18 years; (b) no limitation on the gender; (c) the diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria [1] and confirmed with the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) criteria by trained clinical psychiatrists from each research center; (d) urine sample was available
A total of 117 children with ASD were enrolled in the ASD group, and 119 healthy children were enrolled in the control group
Summary
Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders characterized by social communication difficulties, narrow interests, and repetitive stereotyped behaviors [1]. The prevalence of ASD among children aged 6–12 years is ∼0.70% in China [4]. Early diagnosis remains a challenge for nongenetic ASD, which is mainly based on combining clinician observation with caregiver reports [11]. There is an urgent need to find valuable biomarkers for the early diagnosis of ASD. Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. There is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-center study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms
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