Autistic children's abnormal metabolic profile findings

Chronic biochemical imbalance is often a primary factor in the development of many complex diseases but a possible
metabolic basis for autism has not been well explored. Now Arkansas Children's Hospital Research Institute researchers report
for the first time that children with autism have a severely abnormal metabolic profile indicating increased vulnerability to
oxidative stress. The scientists also identified a significant increase in the frequency of several genetic polymorphisms
that they believe may increase the risk of autism in specific combinations yet to be determined.


Dr. S. Jill James, Professor of Pediatrics at the University of Arkansas for Medical Sciences College of Medicine, presented
the study Saturday, April 2, at the American Society for Nutritional Sciences scientific sessions at Experimental Biology
2005 in San Diego.


Autism is a neurodevelopment disorder characterized by impairment in social interactions, limited language acquisition,
repetitive behaviors, and restricted interests. Usually diagnosed before the age of three, the disorder appears to have
increased tenfold over the last 15 years, now affecting more than 30 of every 10,000 children in the United States. Although
both genetic and environmental factors are believed to contribute to the development of autism, no firm causal evidence
exists. And with no available physiological or biochemical markers, diagnosis currently is made entirely on a behavioral
basis.


Dr. James and colleagues measured plasma levels of the major intracellular antioxidant glutathione and its metabolic
precursors in 95 autistic children and 75 children without autism. Glutathione levels (and also the ratio of reduced to
oxidized glutathione or redox ratio) were significantly decreased in the autistic children, indicating presence of a
significant level of oxidative stress. Oxidative stress occurs when the antioxidant system fails to counteract the generation
or exposure to free radicals. Unopposed free radicals can damage sensitive cells in the brain, the gastrointestinal tract,
and the immune system, and the researchers believe they may contribute to the neurological, gastrointestinal and immunologic
pathology that occurs in autistic children.


Working with a larger number of autistic (360) and non-autistic controls (205), the researchers then looked at common
polymorphisms in genes that could directly or indirectly affect these metabolic pathways and induce oxidative stress. Three
(the catecho-O-methyltransferase gene, the transcobalamin II gene, and the glutathione-S-transferase M1 gene) were found to
be significantly elevated in the autistic children. These genes are prevalent in the general population, says Dr. James, and
clearly do not "cause" autism. However, she and her colleagues believe specific combinations of these and additional genetic
changes could promote the chronic metabolic imbalance seen in the children and thus increase the risk of the disorder.



The next step, says Dr. James, is to determine whether the metabolic profile discovered by the researchers could be used as a
diagnostic test for autism to support the purely behavioral diagnosis currently in use. It also would be important, she says,
to determine whether the abnormal profile is present in high-risk children, such as toddler siblings of autistic children
and/or toddlers with developmental delays.


Dr. James' coauthors are Dr. Stephan Melnyk and Ms. Stefanie Jernigan in her Biochemical Genetics Laboratory at Arkansas
Children's Hospital Research Institute and The University of Arkansas for Medical Sciences.


Contact: Sarah Goodwin

ebpressbellsouth

770-270-0989

Federation of American Societies for Experimental Biology

faseb