Urinary metabolomics using gas chromatography-mass spectrometry: potential biomarkers for autism spectrum disorder

Abstract

Background Diagnosis of autism spectrum disorder (ASD) is generally made phenotypically and the hunt for ASD-biomarkers continues. The purpose of this study was to compare urine organic acids profiles of ASD versus typically developing (TD) children to identify potential biomarkers for diagnosis and exploration of ASD etiology. Methods This case control study was performed in the Department of Pathology and Laboratory Medicine in collaboration with the Department of Pediatrics and Child Health, Aga Khan University, Pakistan. Midstream urine was collected in the first half of the day time before noon from the children with ASD diagnosed by a pediatric neurologist based on DSM-5 criteria and TD healthy controls from August 2019 to June 2021. The urine organic acids were analyzed by Gas Chromatography-Mass Spectrometry. To identify potential biomarkers for ASD canonical linear discriminant analysis was carried out for the organic acids, quantified in comparison to an internal standard. Results A total of 85 subjects were enrolled in the current study. The mean age of the ASD (n = 65) and TD groups (n = 20) was 4.5 ± 2.3 and 6.4 ± 2.2 years respectively with 72.3% males in the ASD group and 50% males in the TD group. Parental consanguinity was 47.7 and 30% in ASD and TD groups, respectively. The common clinical signs noted in children with ASD were developmental delay (70.8%), delayed language skills (66.2%), and inability to articulate sentences (56.9%). Discriminant analysis showed that 3-hydroxyisovalericc, homovanillic acid, adipic acid, suberic acid, and indole acetic were significantly different between ASD and TD groups. The biochemical classification results reveal that 88.2% of cases were classified correctly into ASD& TD groups based on the urine organic acid profiles. Conclusion 3-hydroxy isovaleric acid, homovanillic acid, adipic acid, suberic acid, and indole acetic were good discriminators between the two groups. The discovered potential biomarkers could be valuable for future research in children with ASD.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort

“…Finally, several of the nominally significant metabolites have previously been linked to autism. Altered products of gut bacterial tryptophan metabolism have previously been reported in children with autism 63 . In our study this was reflected by increased levels of indole-3-acetic acid and indole-3-carboxaldehyde.…”

The Difference of Gut Microbiota and Their Correlations With Urinary Organic Acids Between Autistic Children With and Without Atopic Dermatitis

“…This pathway could be augmented when mitochondrial function was impaired. Compared to healthy controls, the increase of adipic acid in urine was significantly correlated with ASD and its severity ( Puig-Alcaraz et al., 2016 ; Khan et al., 2022 ). Furthermore, in the correlation analysis, aconitic acid and adipic acid were positively related.…”

Colorimetric Readout Based Photoionization Detector for Gas Chromatographs

“…Changes in plasma color indicate that it is visually possible to detect different VOCs. It worth noting that the plotting of chromatographic peaks still requires brightness calculation using (1). Note that the attachment of a GC column to the plasma chamber resulted in a different baseline intensity due to a lower flow rate of helium through the device.…”

“…Gas chromatography (GC) has been extensively used in various analytical chemistry applications, including biological science [1], environmental monitoring [2], and the chemical industry [3]. Nevertheless, conventional benchtop GC instruments are bulky, require high power, and are expensive.…”