Metabolomic profiles in serum uncover novel biomarkers in children with Williams–Beuren syndrome

Williams-Beuren syndrome (WBS, OMIM-no.194050) is a rare congenital genetic disorder primarily marked by developmental delays and cardiovascular anomalies, with potential involvement of metabolic dysregulation. Despite this, the metabolic features of WBS have not been extensively studied. Thus, our objective was to examine the serum metabolome profile in children with WBS, elucidating metabolic changes and associated pathways in the disorder. We recruited 25 children with WBS (mean age 5.0 ± 2.6 years, 40% female) from the Children's Hospital affiliated to Zhejiang University between 2020 and 2023. An age and sex matched healthy control group (N = 25) were recruited from the Health Management Center in the same hospital. Clinical information of WBS were extracted from the medical records. Blood samples were obtained for untargeted metabolomics analysis using UPLC-MS/MS. The metabolomic profiles of WBS patients were compared to those of healthy controls to identify metabolites with differential abundance. Enrichment analysis was conducted to identify potentially impacted KEGG pathways. Associations between metabolites and phenotypes were evaluated. Children with WBS exhibited a unique metabolic profile compared to healthy controls, as evidenced by the identification of 465 untargeted metabolites in serum. Of these metabolites, 169 showed differential abundance in WBS children. The top enriched KEGG pathways in WBS children included nicotine addiction, cholesterol metabolism, arginine biosynthesis, retrograde endocannabinoid signaling. Additionally, there were indications of potential metabolic alterations in the L-tryptophan pathway, with a shift from serotonin to L-kynurenine, as well as disruptions in bile acid metabolism. Metabolome data in children with WBS showed neurological and amino acid metabolism changes, indicating multisystem involvement and developmental delay. This data can help monitor and manage the disease, but further studies are needed to understand the underlying mechanisms and consequences.