This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Autism is a complex neurodevelopmental disorder. There are currently no scientifically validated medical treatments for autism, however, there are many complimentary and alternative therapies. Gastrointestinal symptoms have been reported in 15-20% of children with autism spectrum disorders and many theories about the cause of autism arise from GI related issues. The lay literature recommends using a gluten and casein free diet in children with autism based on the 'opiod theory.' In this theory milk (casein) and wheat (gluten) proteins are incompletely broken down in the intestine, absorbed by a 'leaky gut' and exert an 'opioid-like' effect in the brain. The only supporting evidence for increased intestinal permeability in children with autism was reported by D'Eufemia in a small population of children with autism(1). In a study of children with high functioning autism without gastrointestinal symptoms, D'Eufemia, et al found abnormal intestinal permeability in 9 of 21 children. Despite the lack of scientific data to support the gluten and casein free diet, many families put their children on the diet. This is probably due to the fact that there is no cure for autism. The diet is difficult to follow, expensive and time consuming. Accurate information is very important for the families of children with autism, so that they may make well informed decisions about interventions for their children. This study will be a more comprehensive assessment of intestinal permeability. Two groups of subjects with autism spectrum disorders (ASD) will be compared to control subjects. Thirty-seven subjects with ASD on a gluten and casein free diet and 37 subjects on an unrestricted diet will be enrolled. It is unlikely that diet will effect intestinal permeability but gluten does increase intestinal permeability in individuals with celiac disease, therefore both groups will be included seperatedly. A group of 37 should give adequate power to detect a statistically significant difference between groups. This study will test for serum autoantibodies found in celiac disease which is a disorder of the small intestine associated with increased intestinal permeability and sensitivity to gluten. Celiac disease can be asymptomatic and may occur in as many as 1% of the general population. Serum zonulin levels will also be evaluated as zonulin has been associated with abnormal intestinal tight junctions and may affect intestinal permeability. Subjects will have a research reliable diagnosis of autism and will complete questionnaires regarding gastrointestinal symptoms and keep a 7 day stool record. Thirty-seven control subjects with typical development will be recruited for the intestinal permeability study and questionnaires only. Control subjects will have blood drawn for tissue transglutaminase only if their intestinal permeability study is abnormal.

National Institute of Health (NIH)
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General Clinical Research Centers Program (M01)
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University of Colorado Denver
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