There has been much research into autism or autistic spectrum disorder (ASD) and room for considerable conjecture regarding the etiology of these disorders remain. ASD is marked by a complex interaction between environmental factors and genetic predisposition, including epistasis. This manuscript argues that changes in oxidative metabolism, thiamine homeostasis, heavy metal deposition and cellular immunity have a role in the etiopathogenesis of autism and ASD. Recent evidence for abnormal thiol metabolism, marked by significant alteration in the deposition of several trace heavy metal species is provided here. We hypothesize that altered thiol metabolism from heavy metal toxicity, one of the key mechanisms for oxidative stress production, may be responsible for the biochemical alterations in transketolase, dysautonomia and abnormal thiamine homeostasis. It is unknown why these particular metals accumulate; but we suspect that children with ASD and forms of autism may have particular trouble excreting thiol-toxic heavy metal species. We maintain divalent cation accumulation is evidence of altered clearance, which leads to oxidative stress, offering intriguing component or possible mechanism for oxidative stress-mediated neurodegeneration in ASD patients.