make our meta-analyses a prominent component of the review, but rather to use the data to identify the extent of confounding and selection biases and to examine possible sources of heterogeneity between the results of individual observational studies. Only two of the reviewed studies corrected for multiple comparisons (e.g. Bonferroni or Nyholt correction) [ 86 , 97 ]. The few studies that matched cases with controls did not use a paired method of analysis such as McNemar's test which biases the results towards null. Further, we were unable to replicate the p values for three studies [ 46 , 47 , 87 ]. Conclusions This review of published studies indicates that evidence for the involvement of the ?-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders should be further explored with higher quality and lower risk bias studies to in order to ascertain the significance of these pathways with respect to clinical outcomes. Trends noted from currently published studies include decreased total glutathione and increased GSSG in children with autism spectrum disorders with no association found between homocysteine or cystathione in these children. There is a trend for cysteine to be lower in children with autistic disorder but not in other autism spectrum disorders. There is a need for large, well designed studies that link metabolites, co-factors and genes of the ?-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes to be conducted in children with autism spectrum disorders. Future risk factor analysis of autism spectrum disorders should include consideration