Bai Guannan, Chen Weijun, Ji Chai, Yang Yang, Shen Jiyang, Li Fangfang, Wen Yang, Tan Danny Junyi, Jiang Xiaoling, Xiao Yingping, Chen Jinluan
Department of Child Health Care, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, Zhejiang Province, China.
Yunnan Provincial Key Laboratory of Public Health and Biosafety & School of Public Health, Kunming, Yunnan Province, People's Republic of China.
Sci Rep. 2025 Mar 19;15(1):9437. doi: 10.1038/s41598-025-94018-w.
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.
威廉姆斯-贝伦综合征（WBS，OMIM编号：194050）是一种罕见的先天性遗传疾病，主要特征为发育迟缓、心血管异常，可能还伴有代谢失调。尽管如此，WBS的代谢特征尚未得到广泛研究。因此，我们的目标是研究WBS患儿的血清代谢组学特征，阐明该疾病中的代谢变化及相关途径。2020年至2023年期间，我们从浙江大学附属儿童医院招募了25名WBS患儿（平均年龄5.0±2.6岁，40%为女性）。从同一家医院的健康管理中心招募了年龄和性别匹配的健康对照组（N = 25）。从病历中提取WBS的临床信息。采集血样用于超高效液相色谱-串联质谱（UPLC-MS/MS）的非靶向代谢组学分析。将WBS患者的代谢组学特征与健康对照组进行比较，以鉴定丰度有差异的代谢物。进行富集分析以鉴定可能受影响的京都基因与基因组百科全书（KEGG）途径。评估代谢物与表型之间的关联。与健康对照组相比，WBS患儿表现出独特的代谢特征，血清中鉴定出465种非靶向代谢物可证明这一点。在这些代谢物中，169种在WBS患儿中显示出丰度差异。WBS患儿中富集程度最高的KEGG途径包括尼古丁成瘾、胆固醇代谢、精氨酸生物合成、逆行性内源性大麻素信号传导。此外，有迹象表明色氨酸途径存在潜在的代谢改变，从血清素向L-犬尿氨酸转变，以及胆汁酸代谢紊乱。WBS患儿的代谢组学数据显示神经和氨基酸代谢发生变化，表明多系统受累和发育迟缓。这些数据有助于监测和管理该疾病，但需要进一步研究以了解潜在机制和后果。
