Autism, a neurodevelopment disorder which has increased tenfold over the last 15 years, now affects 30 of every 10,000 children in the United States.
It is characterized by impaired in social interaction, limited language acquisition, repetitive behaviours, and restricted interests and is usually diagnosed before a child reaches the age of three. Genetic and environmental factors are believed to contribute to the development of autism, but there is as yet little evidence to support this theory. Diagnosis is usually made on a behavioural basis.
Chronic biochemical imbalance is often a factor in the initial development of many complex diseases but a possible metabolic imbalance in cases of autism has not been properly researched until now.
Dr. S. Jill James, Professor of Paediatrics at the University of Arkansas for Medical Sciences College of Medicine and researchers at Arkansas Children's Hospital Research Institute have found that children with autism have a severely abnormal metabolic profile which suggests an increased vulnerability to oxidative stress. They also found a significant increase in the frequency of several genetic polymorphisms that they believe, in specific combinations, may increase the risk of autism.
Dr. James and colleagues measured plasma levels of the major intracellular antioxidant glutathione and its metabolic precursors in 170 children, 95 with autism, and 75 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.
When they looked at a larger number of autistic (360) and non-autistic controls (205), and studied common polymorphisms in genes that could affect the metabolic pathways and induce oxidative stress, they found that particular genes were found to be significantly elevated in the autistic children, (the catecho-O-methyltransferase gene, the transcobalamin II gene, and the glutathione-S-transferase M1 gene). As many of us have these genes they clearly do not "cause" autism says Dr. James, but she and her colleagues believe specific combinations of these and additional genetic changes could promote the chronic metabolic imbalance seen in the children and increase the risk of the disorder.
Dr. James says the next step, is to find out if the metabolic profile discovered by the researchers could be used as a diagnostic test for autism to support the purely behavioural diagnosis currently in use. It also would also be important in determining 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' co-authors 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.The study was presented at the American Society for Nutritional Sciences scientific sessions at Experimental Biology 2005 in San Diego on April 2nd.