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Amino acid dysregulation metabotypes help diagnose a subset of ASD earlier

Findings published in Biological Psychiatry reported that amino acid dysregulation metabotypes may offer a way to diagnose a subset of children with autism spectrum disorder earlier.

The researchers could detect about 17% of children with ASD with this panel of alterations in amino acid metabolism, David G. Amaral, PhD, Beneto Foundation Chair of the MIND Institute and professor in the psychiatry and behavioral sciences department at University of California Davis, said in a press release.

“In the United States, children are typically diagnosed with autism when they are more than 4 years old on average. However, the best option for decreasing the debilitating effects of autism is early intensive behavioral therapy — and the earlier the better,” Amaral told Healio Psychiatry. “It would be ideal if children would be diagnosed at a much earlier age so that they could receive effective therapy as soon as possible. The blood tests under study may provide important indicators of risk for autism.”

Currently, no reliable diagnostic biomarkers exist for ASD; however, prior evidence has shown that dysregulation of branch chain amino acids may contribute to the behavioral characteristics of autism. In their paper, the researchers reported results from the Children’s Autism Metabolome Project, a large-scale study to identify autism biomarkers using metabolomic analyses of blood samples from children.

The investigators identified dysregulation of amino acid metabolism by comparing plasma metabolites from 516 children with ASD aged 18 months to 4 years with those from 164 age-matched typically-developing children recruited into the Project. Based on shared metabolic phenotypes linked to brain chain amino acid dysregulation, they stratified children with ASD into subpopulations.

Amaral and colleagues identified groups of amino acids that were negatively correlated with brain chain amino acid levels in autism.

Disparities between these groups of amino acids detected three autism-associated amino acid dysregulation metabotypes, according to the study findings. In combination, these three associated amino acid dysregulation metabotypes — glutamine, glycine and ornithine — identified a dysregulation in amino acid/brain chain amino acid metabolism present in 16.7% of the participants with ASD. This was detectable with a specificity of 96.3% and a positive predictive value of 93.5%, the results showed.

"It is unlikely that a single marker will detect all autism. This paper demonstrates that alterations in metabolic profiles can detect sizable subsets of individuals with autism,” Amaral said in the release. “The hope is that we will be able to generate a panel of biomarkers that will detect a large proportion of people at risk. Moreover, this approach highlights metabolic pathways that may be targets of intervention."

“There are different types of autism that have different metabolic profiles. Using metabolomics will provide clinicians with additional information to validate their diagnosis of autism and potentially provide information on the most effective forms of therapy,” he told Healio Psychiatry. – by Savannah Demko

Disclosure: Amaral reports funding from the NIH, the Simons Foundation and Stemina Biomarker Discovery, Inc. He also reports serving on the scientific advisory boards for Axial Therapeutics and Stemina Biomarker Discovery. Please see the study for all other authors’ relevant financial disclosures.