Autism spectrum disorder (ASD) diagnosis: A biochemical investigation into the diagnostic utility of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) levels and the SAM/SAH ratio

Abstract

Background

The balance between SAM and SAH ratios is critical for cellular methylation capacity such that a decrease in this ratio signals decrease the methylation potential, impacting cellular functions. In Autism Spectrum Disorder (ASD), impaired methylation processes are prominent, disrupting essential methyl group transfers crucial for DNA methylation, neurotransmitter synthesis, and detoxification. This disturbance affects gene expression and neural function, contributing to ASD development. This paper aims to explore ASD's pathogenesis by investigating biochemical parameters linked to the methylation cycle. For this purpose, some laboratory parameters are employed to aid in the understanding of potential laboratory abnormalities in ASD in children aged 2 to 8 years.

Materials and Methods

This study included a cohort of 43 children aged 2 to 8 years diagnosed ASD, alongside a control group of 43 age-and gender-matched healthy subjects. The serum of blood samples taken was used to measure biochemical factors. Specimens were processed using ELISA instrumentation and hemogram auto analyzers. The study conducted a statistical comparison between the ASD-diagnosed subjects and healthy controls, focusing on levels of S-adenosyl methionine (SAM), S-adenosyl homocysteine (SAH), Glycine N-methyltransferase (GNMT), and platelet counts.

RESULTS

The levels of SAH and platelets were significantly higher in the case group compared to the control group. Conversely, levels of SAM, as well as the SAM/SAH ratio, were found to be significantly lower in the case group than in the control group (p < 0.05). No statistically significant difference was observed in the levels of GNMT when compared (p > 0.05). Receiver Operating Characteristic (ROC) analysis revealed that the diagnostic performance for SAM had an area under the curve (AUC) of 0.876, with a cut-off point determined at 286.9 ng/mL, yielding a sensitivity of 85 % and a specificity of 75 %. For SAH, the AUC was calculated to be 0.671, with a cut-off point set at 0.49 ng/mL, resulting in a sensitivity and specificity of 64 %. The SAM/SAH ratio demonstrated an AUC of 0.806, with the cut-off point established at 576.3, leading to a sensitivity and specificity of 72 %. A significant negative correlation was detected between the scores of the Modified Checklist for Autism in Toddlers (M-CHAT) and both SAM levels and the SAM/SAH ratio. The analysis indicated that an increase of one unit (1 ng/mL) in SAM levels is associated with a decreased autism risk by a factor of 1/0.914 = 1.1 %, whereas an increase of one unit (1 × 10³/µL) in platelet count is associated with an increased autism risk by a factor of 1.019 %. Regarding glycine N-methyltransferase, no significant difference was observed between the two groups.

Conclusion

Follow-up studies with larger samples will be needed to better understand the potential for SAM, SAH, and SAM/SAH as a potential biomarker, at least for a subset of those with ASD. The correlation between these markers and the total score on the M-Chat raises further interest in this possibility. The correlation between these markers and the total score on the M-Chat further supports their utility as clinical biochemical laboratory parameters that could aid in the diagnosis of ASD.