Abstract

Several studies have linked branched-chain amino acid (BCAA) metabolism disorders with autism spectrum disorder (ASD), but the results have been inconsistent. The purpose of this study was to explore the association between BCAA concentrations and the risk of ASD. A total of 313 participants were recruited from two tertiary referral hospitals from May 2018 to July 2021. Concentrations of BCAAs in dried blood spots were analyzed using liquid chromatography-tandem mass spectrometry-based analysis. Multivariate analyses and restricted cubic spline models were used to identify the association between BCAAs and the risk of ASD, and a nomogram was developed by using multivariate logistic regression and the risk was determined by receiver operating characteristic curve analysis and calibration curve analysis. Concentrations of total BCAA, valine, and leucine/isoleucine were higher in the ASD group, and all of them were positively and non-linearly associated with the risk of ASD even after adjusting for potential confounding factors such as age, gender, body mass index, and concentrations of BCAAs (P < 0.05). The nomogram integrating total BCAA and valine showed a good discriminant AUC value of 0.756 (95% CI 0.676–0.835). The model could yield net benefits across a reasonable range of risk thresholds. In the stratified analysis, the diagnostic ability of the model was more pronounced in children older than 3 years. We provide evidence that increased levels of BCAAs are associated with the risk of ASD, and the nomogram model of BCAAs presented here can serve as a marker for the early diagnosis of ASD.

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