Background: Genetic risk factors play an important role in neurological disorders. In this case-control study, we examined the C677T polymorphism (rs1801133) in the Methylenetetrahydrofolate reductase (MTHFR) gene and its association with three neurodegenerative disorders: The late onset pathology, Alzheimer disease and two early onset ones, Autism and Down syndrome. New evidence suggests that autism may be associated with varied behavioural responses to folate therapy and metabolic anomalies, including those in folate metabolism, that contribute to hypomethylation of DNA. We hypothesis that, MTHFR C677T mutation may be the underlying common risk factor in various neurological disorders leading to impaired one carbon metabolism resulting in similar and severe neuropsychological symptoms. Hence our objective was to evaluate MTHFR C677T polymorphism in different Neurological disorders and compare it with age-matched healthy controls.Method: This case-control study was carried out on 200 samples which included 100 patients with different neurological disorders and 100 healthy individuals without any neurological problems taken as the control group. MTHFR polymorphism was assessed by PCR-RFLP. Results:Results indicated that the C677T MTHFR polymorphism was not significantly different between controls of younger and older age groups. Among the three neurological disorders studied the T allele was associated with autism (TT+CT vs. CC; OR=4.472, 95% CI: 1.605-12.799, p<0.002), but not with the other two conditions. Conclusion:In conclusion, despite the smaller sample size, the C677T polymorphism of MTHFR plays a role in some complex neurodevelopmental disorders and not in others.