Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study
Background: X-linked hypophosphatemia (XLH) is a rare disorder characterized by elevated levels of fibroblast growth factor 23 (FGF-23), leading to hypophosphatemia and complications in diagnosis due to its clinical heterogeneity. Metabolomic analysis, which examines metabolites as the final product...
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2024-12-01
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| author | Luis Carlos López-Romero José Jesús Broseta Marta Roca-Marugán Noemí Máñez Ramírez Julio Hernández-Jaras |
| author_facet | Luis Carlos López-Romero José Jesús Broseta Marta Roca-Marugán Noemí Máñez Ramírez Julio Hernández-Jaras |
| author_sort | Luis Carlos López-Romero |
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| description | Background: X-linked hypophosphatemia (XLH) is a rare disorder characterized by elevated levels of fibroblast growth factor 23 (FGF-23), leading to hypophosphatemia and complications in diagnosis due to its clinical heterogeneity. Metabolomic analysis, which examines metabolites as the final products of cellular processes, is a powerful tool for identifying in vivo biochemical changes, serving as biomarkers of pathological abnormalities, and revealing previously uncharted metabolic pathways. Methods: A multicenter cross-sectional case-control study of adult patients diagnosed with XLH was conducted. Serum metabolomic analysis was performed with an Ultra-Performance Liquid Chromatography equipment (UPLC) coupled to a high-resolution mass spectrometer (MS). An analysis of metabolic pathways using MetaboAnalyst version 5.0 and a quantitative enrichment analysis (QEA) was performed. We employed multivariate statistical models, including a principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) regression model. Results: A cohort of 20 XLH patients and 19 control subjects were recruited. A total of 104 metabolites were identified. The differential metabolites identified included glycine, taurine, hypotaurine, phosphoethanolamine, pyruvate, guanidoacetic acid, serine, succinate, 2-aminobutyric acid, glutamine, 2-hydroxyvaleric acid, methionine, ornithine, phosphorylcholine, hypoxanthine, lysine, and N-methylnicotinamide. Enrichment analysis identified disturbances in key metabolic pathways, including phosphatidylethanolamine biosynthesis, sphingolipid metabolism, and phosphatidylcholine biosynthesis. Additionally, pathways related to cysteine metabolism, glycolysis, and pyruvate metabolism. Conclusions: This study identified significant differences in the metabolic profiles of individuals with XLH compared to healthy controls. These findings enhance understanding of potential pathogenic mechanisms and offer a metabolic basis for further in-depth investigations into XLH. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
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| series | Biomedicines |
| spelling | doaj-art-ea545de14c9845cdae90d43f55a3c35a2025-01-24T13:23:45ZengMDPI AGBiomedicines2227-90592024-12-011312210.3390/biomedicines13010022Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control StudyLuis Carlos López-Romero0José Jesús Broseta1Marta Roca-Marugán2Noemí Máñez Ramírez3Julio Hernández-Jaras4Department of Nephrology, Hospital de Manises, 46940 Valencia, SpainDepartment of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, 08036 Barcelona, SpainMetabolomics Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, SpainDay Hospital Hematology and Oncology, Nursing Service, Hospital Universitari i Politècnic La Fe, 46026 Valencia, SpainDepartment of Nephrology, Hospital Universitari i Politècnic La Fe, 46026 Valencia, SpainBackground: X-linked hypophosphatemia (XLH) is a rare disorder characterized by elevated levels of fibroblast growth factor 23 (FGF-23), leading to hypophosphatemia and complications in diagnosis due to its clinical heterogeneity. Metabolomic analysis, which examines metabolites as the final products of cellular processes, is a powerful tool for identifying in vivo biochemical changes, serving as biomarkers of pathological abnormalities, and revealing previously uncharted metabolic pathways. Methods: A multicenter cross-sectional case-control study of adult patients diagnosed with XLH was conducted. Serum metabolomic analysis was performed with an Ultra-Performance Liquid Chromatography equipment (UPLC) coupled to a high-resolution mass spectrometer (MS). An analysis of metabolic pathways using MetaboAnalyst version 5.0 and a quantitative enrichment analysis (QEA) was performed. We employed multivariate statistical models, including a principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) regression model. Results: A cohort of 20 XLH patients and 19 control subjects were recruited. A total of 104 metabolites were identified. The differential metabolites identified included glycine, taurine, hypotaurine, phosphoethanolamine, pyruvate, guanidoacetic acid, serine, succinate, 2-aminobutyric acid, glutamine, 2-hydroxyvaleric acid, methionine, ornithine, phosphorylcholine, hypoxanthine, lysine, and N-methylnicotinamide. Enrichment analysis identified disturbances in key metabolic pathways, including phosphatidylethanolamine biosynthesis, sphingolipid metabolism, and phosphatidylcholine biosynthesis. Additionally, pathways related to cysteine metabolism, glycolysis, and pyruvate metabolism. Conclusions: This study identified significant differences in the metabolic profiles of individuals with XLH compared to healthy controls. These findings enhance understanding of potential pathogenic mechanisms and offer a metabolic basis for further in-depth investigations into XLH.https://www.mdpi.com/2227-9059/13/1/22X-linked hypophosphatemiaXLHmetabolitesmetabolomicstubulopathyhypophosphatemia |
| spellingShingle | Luis Carlos López-Romero José Jesús Broseta Marta Roca-Marugán Noemí Máñez Ramírez Julio Hernández-Jaras Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study Biomedicines X-linked hypophosphatemia XLH metabolites metabolomics tubulopathy hypophosphatemia |
| title | Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study |
| title_full | Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study |
| title_fullStr | Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study |
| title_full_unstemmed | Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study |
| title_short | Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study |
| title_sort | comprehensive metabolomic profiling in adults with x linked hypophosphatemia a case control study |
| topic | X-linked hypophosphatemia XLH metabolites metabolomics tubulopathy hypophosphatemia |
| url | https://www.mdpi.com/2227-9059/13/1/22 |
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