Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study
Luis Carlos López-Romero1, José Jesús Broseta2, Marta Roca-Marugán3
1Department of Nephrology, Hospital de Manises, 46940 Valencia, Spain.
Biomedicines
|January 25, 2025
Summary
Metabolomic analysis reveals distinct metabolic profiles in X-linked hypophosphatemia (XLH) patients, identifying key differences in metabolites and pathways compared to healthy individuals. This deepens understanding of XLH pathogenesis.
Area of Science:
- Biochemistry
- Genetics
- Metabolomics
Background:
- X-linked hypophosphatemia (XLH) is a rare genetic disorder causing hypophosphatemia due to elevated fibroblast growth factor 23 (FGF-23).
- Clinical diagnosis of XLH is complicated by its heterogeneity.
- Metabolomic analysis offers a powerful approach to identify biomarkers and understand biochemical changes in diseases.
Purpose of the Study:
- To investigate the serum metabolomic profile of adult patients with X-linked hypophosphatemia (XLH).
- To identify differential metabolites and altered metabolic pathways in XLH.
- To provide a metabolic basis for understanding XLH pathogenesis.
Main Methods:
- A multicenter, cross-sectional case-control study involving 20 XLH patients and 19 healthy controls.
- Serum samples analyzed using Ultra-Performance Liquid Chromatography (UPLC) coupled with high-resolution mass spectrometry (MS).
- Metabolic pathway analysis performed using MetaboAnalyst 5.0 with quantitative enrichment analysis (QEA) and multivariate statistical models (PCA, OPLS-DA).
Main Results:
- 104 metabolites were identified, with significant differences found between XLH patients and controls.
- Differential metabolites included glycine, taurine, pyruvate, serine, succinate, and others.
- Enrichment analysis revealed disturbances in phosphatidylethanolamine biosynthesis, sphingolipid metabolism, phosphatidylcholine biosynthesis, cysteine metabolism, glycolysis, and pyruvate metabolism.
Conclusions:
- Significant differences in metabolic profiles distinguish XLH patients from healthy controls.
- These findings contribute to understanding the pathogenic mechanisms of XLH.
- The study provides a metabolic foundation for future XLH research.
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