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Updated: Aug 27, 2025
Testing Sensory and Multisensory Function in Children with Autism Spectrum Disorder
Published on: April 22, 2015
Urinary Untargeted Metabolic Profile Differentiates Children with Autism from Their Unaffected Siblings
Anna Maria Timperio1, Federica Gevi1, Francesca Cucinotta2,3
1Department of Ecological and Biological Sciences, University of Tuscia, 01100 Viterbo, Italy.
Insights
Autism Spectrum Disorder (ASD) is linked to metabolic imbalances in purine and tryptophan pathways. Gut bacteria metabolites are elevated in children with ASD, suggesting a potential diagnostic marker.
Area of Science:
- Metabolomics
- Neurodevelopmental Disorders
- Genetics and Genomics
Background:
- Autism Spectrum Disorder (ASD) presents significant heterogeneity in causes and symptoms.
- Previous research identified metabolic imbalances in purine, tryptophan, and amino acid metabolism, along with vitamin deficiencies in children with ASD.
- Intestinal flora-derived compounds were also implicated in prior studies of ASD.
Purpose of the Study:
- To identify reliable metabolic fingerprints associated with ASD by analyzing urinary metabolomic differences within families.
- To replicate and extend previous findings on metabolic perturbations in ASD using a tightly matched sibling design.
- To investigate the potential of gut microbiota-derived compounds as diagnostic markers for ASD.
Main Methods:
- Urinary metabolomic analysis was performed on 14 pairs of children with idiopathic ASD and their typically developing siblings, matched for age and sex.
- A sensitive and unbiased approach was employed for broad metabolite detection in urine.
- Multivariate statistical analysis was used to identify significant metabolic differences.
Main Results:
- Significant perturbations in purine and tryptophan pathways were replicated, confirming previous findings.
- Abnormalities in the phenylalanine, tyrosine, and tryptophan pathway were highlighted, with increased phenylalanine and decreased tyrosine levels observed.
- Elevated concentrations of bacterial degradation products, including phenylpyruvic acid, phenylacetic acid, and 4-ethylphenyl-sulfate, were found in children with ASD.
Conclusions:
- Metabolic imbalances, particularly in amino acid and gut microbiota pathways, are strongly linked to ASD, independent of environmental factors.
- Excessive gut microbiota-derived compounds in ASD may serve as valuable diagnostic indicators within a network model.
- A 'metabolic autism spectrum' may exist, with unaffected siblings potentially showing intermediate metabolic profiles, suggesting an endophenotype.
Abstract:
Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to the metabolism of purines, tryptophan and other amino acids, as well as compounds derived from the intestinal flora, and reduced levels of vitamins B6, B12 and folic acid. The present study describes significant urinary metabolomic differences within 14 pairs, including one child with idiopathic ASD and his/her typically-developing sibling, tightly matched by sex and age to minimize confounding factors, allowing a more reliable identification of the metabolic fingerprint related to ASD. By using a highly sensitive, accurate and unbiased approach, suitable for ensuring broad metabolite detection coverage on human urine, and by applying multivariate statistical analysis, we largely replicate our previous results, demonstrating a significant perturbation of the purine and tryptophan pathways, and further highlight abnormalities in the "phenylalanine, tyrosine and tryptophan" pathway, essentially involving increased phenylalanine and decreased tyrosine levels, as well as enhanced concentrations of bacterial degradation products, including phenylpyruvic acid, phenylacetic acid and 4-ethylphenyl-sulfate. The outcome of these within-family contrasts consolidates and extends our previous results obtained from unrelated individuals, adding further evidence that these metabolic imbalances may be linked to ASD rather than to environmental differences between cases and controls. It further underscores the excess of some gut microbiota-derived compounds in ASD, which could have diagnostic value in a network model differentiating the metabolome of autistic and unaffected siblings. Finally, it points toward the existence of a "metabolic autism spectrum" distributed as an endophenotype, with unaffected siblings possibly displaying a metabolic profile intermediate between their autistic siblings and unrelated typically-developing controls.
