Back ground: Many studies were done on folate , methionine and transsulfuration pathway reported that dysfunctional enzymes of these pathways may play an important role in the pathophysiology of autism. MTHFR is one of the most important enzymes in the folate/ homocysteine pathway. It regulates the intracellular flow of folate. The link between autism, methylation, and the MTHFR gene mutation is lies in, that these mutation leads to deficient synthesise of adequate amounts of some neurotransmitters such as dopamine. Beside this, in view of the fact that C677T and A1298C variants occur at significantly higher rates in those with autism compared to controls . Aim: we aimed to investigate (genotype - phenotype coleration of MTHFR (C677T) polymorphism on autistatic children. Methods: For this purpose we use sequencing technique to investigated C677T in 20 autistic children, 20 control children. Conclusion: This study demonstrates a role for (C667T) mutation in MTHFR gene in the increased risk for Autism Spectrum Disorders (ASD). It also gives a support to complete the study for (C667T) mutation in MTHFR in a wide range on the Egyptian autism population to conclude precise associations.