In Hartnup disease and phenylketonuria (PKU), the cause of the increased levels of IAG in the urine is believed to be purely genetic, but there could be other reasons. Through our associated studies, we have found what appears to be elevated levels of IAG in certain other conditions, in particular, in those experiencing symptoms commonly known as 'Gulf War syndrome'.
At this time, we are investigating the possibility that OP based pesticides may be at least partly responsible for these abnormally elevated levels. Certainly, the US and UK forces deployed in the Gulf would have been exposed to such compounds, as are those suffering from 'sheep dip syndrome' ('fruit pickers syndrome' in the US). All of these individuals experience marked psychological as well as physical effects.
OP compounds were developed as agents of war ('nerve gases') and insecticides because of their ability to cause paralysis by inhibiting certain enzyme systems and, in particular, those involving anticholinesterases, thereby affecting the central nervous system and muscle control. OP compounds tend to be non specific in their actions and may affect other enzyme systems as well.
Most interesting in terms of autism is the effect of OP compounds on the enzymes involved in tryptophan metabolism (Biochem Pharmacol, 1992; 44: 2243-50; Eur J Pharmacol, 1993; 248: 237-41). Diazinon, an OP pesticide, has been reported to seriously interfere with the metabolism of tryp tophan via the kynurenine pathways, an intermediate amino acid in tryptophan metabolism. This, in itself, could be sufficient to push tryptophan metabolism towards producing IAG. If there are also effects on the enzyme tryptophan hydroxylase (which we are currently investigating), then this may be an additional impetus towards creation of the abnormal metabolite IAG.
The Gulf War only lasted a few days, but it was by far the most toxic war in history. In addition to the pesticides (mainly OPs) used by the allies to protect their troops and any which may have been derived from other sources, both troops and civilians were exposed to toxic products from burning oil wells. Soldiers had the additional burden of up to 12 separate vaccinations, some containing the mercury based preservative thimerosal, all administered on the same day. There was also the very strong likelihood that depleted uranium which, in spite of its name, is still radioactive was absorbed. In effect, our soldiers were exposed to all the main forms of modern contamination in combination with an unusually stressful and threatening situation. It would be astonishing if these individuals, given such exposure, returned from the Gulf War with their health intact.
The symptoms of Gulf War syndrome are similar (but not identical) to those seen in myalgic encephalitis (chronic fatigue syndrome). As with autism, the appearance of the symptoms might be explained by the combined effects of environmental factors, such as pesticides, and infections, which may be natural or induced through vaccines on individuals of varying genetic fragility.
Another line of evidence which points to a similar cause between the two syndromes is the reported usefulness of dietary interventions, specifically, elimination of gluten and casein. This has been shown in several studies to ameliorate some of the symptoms of Gulf War syndrome and other forms of autism (Autism, 1999; 3: 45-69) and is supported by personal reports at our own institution.