Methionine cycle imbalance in children with multifactorial forms of autism spectrum disorders: a clinical and laboratory study

Autism spectrum disorders are characterized by marked heterogeneity. Standard clinical classification does not reflect the metabolic characteristics of patients, which limits the possibilities of laboratory stratification and a pathogenetically focused approach to treatment. One of the key biochemical pathways potentially involved in the pathogenesis of idiopathic forms of autism spectrum disorders is the methionine cycle and one-carbon metabolism.

The aim of the study. To evaluate methionine cycle parameters in children with non-syndromic and idiopathic forms of autism spectrum disorders and determine their clinical and diagnostic significance.

Materials and methods. A cross-sectional comparative study was conducted involving 65 children with multifactorial autism spectrum disorders (divided by the severity of autism spectrum disorders into 3 subgroups according to DSM-5: ASD Level 1, ASD Level 2, ASD Level 3) aged 44–72 months and 30 apparently healthy children in the control group. Homocysteine (Hcy), S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy) were determined by liquid chromatography with tandem mass spectrometry. The AdoMet/AdoHcy ratio was calculated as an integral indicator of methylation potential. Statistical analysis included nonparametric methods.

Results. All subgroups of patients showed statistically significant differences from the control group for all indicators of one-carbon metabolism (p<0.001). An increase in homocysteine levels, a decrease in AdoMet concentrations, an accumulation of AdoHcy, and a significant decrease in the AdoMet/AdoHcy ratio were observed. The most pronounced methylation potential disturbances were detected in patients with autism spectrum disorders (ASD Level 3) according to DSM-5. The AdoMet/AdoHcy ratio demonstrated the highest diagnostic specificity among clinical groups.

Conclusion. A systemic methionine cycle imbalance was detected in children with multifactorial autism spectrum disorders. A comprehensive assessment of Hcy, AdoMet, and AdoHcy, as well as calculation of the AdoMet/AdoHcy ratio, can be considered a promising tool for the laboratory diagnosis of autism spectrum disorders in patients and for the justification of pathogenetically targeted metabolic interventions in pediatric practice.

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