Biomarkers in children with Autism: A case control Study

Objectives:Tocompare the levels of methylation pathway biomarkers, advanced glycation end-products and correlate with severity of autism (CARS score), sensory issues (SP2 score), co-morbidities (CBCL score) and DQ/IQ(MISIC/VSMS/BKT) Methods: Children with ASD between 2-18 years fulfilling DSM-5 criteria were selected. Subjects with chronic-illness or those on any antioxidant therapy/multivitamins/anti-epileptic drugs were excluded. Results: 100 cases (male-82) and 50controls (male-41) were enrolled.The frequency of CC,CT and TT genotypes in ASD group was 84%,14% and 2% and in control group was 86%,12% and 2% respectively; thus, C677T polymorphism was not associated with increased ASD risk. The median level of serum homocysteine in ASD group was 9 µmol/L(95% CI: 7-16 µmol/L), was significantly higher than controls 7 µmol/L(95% CI:4-11µmol/L)(p=0.01). The prevalence of hyper-homocystinemia (>15µmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). No significant correlation was found between prevalence of hyper-homocysteinemia and severity of autism/DQ/presence or absence of sensory andbehavioural issues. Among AGEs only dityrosine was found to be significantly elevated in ASD group. No significant difference was found between the median levels of plasma cysteine or methionine, urine uric-acid to creatinine ratio, arterial lactate, serum vitamin E, vitamin B12 and folate. Conclusions: The MTHFR C677T polymorphism is neither a risk nor protective factor. The prevalence of hyperhomocysteinemia is significantly higher in ASD compared to controls and is independent of MTHFR polymorphism and vitamin B12/folate levels. The evidence for the role of increased oxidative stress is also strengthened by the increased dityrosine levels.