Objectives: To study the characteristics of plasma amino acid (PLA) in children with autism spectrum disorder (ASD) and its possibly clinical phenotypes association.

Methods: 110 children diagnosed with ASD, and 55 age and sex matched healthy control were assessed for PLA, via liquid chromatography-tandem mass spectrometry. Methylmalonic acid was detected in both groups to rule out acquired VitB12 deficiency. The clinical phenotypes association of PLA regarding cognition (high vs low function (<70)), severity of autism (mild and moderate vs severe), and regression (non-regression vs regression) was evaluated. The severity of autism was estimated by Childhood Autism Rating Scale, while DQ/IQ was assessed by Gesell Development Diagnosis Scale/Wechsler Preschool and Primary (WPPSI-IV) or Children Scale (WSIC-IV) of Intelligence WSIC-IV.

Results: Autistic children showed significantly elevated glutamic acid, gamma-aminobutyric acid, glutamine, sarcosine, delta-aminolevulinic acid, glycine, hydroxyproline, and citrulline, whereas the plasma level of ethanolamine, phenylalamine, tryptophan, homocysteine, ornithine, histidine, lysine, and glutathione were significantly lower, compared with the healthy control. Reagrding severity of autism, the levels of pipecolic acid and N-glycyl-proline were higher in severe group than in mild and moderate group, while regressive autistic children showed significantly increased proline, sarcosine and gluthione level. No significant difference of plasma level of amino acid between high and low function group was found.

Conclusion: Elevated neuroactive amino acids (glutamic acid, gamma-aminobutyric acid, glutamine, glycine) and decreased essential amino acids (phenylalamine, tryptophan, lysine) exhibit distinct characteristics of autistic children. Elevated proline and N-glycyl-proline may be associated with the severity of autism and regressive features respectively.