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Parsing Fabry Disease Metabolic Plasticity Using Metabolomics
Franklin Ducatez1,2, Wladimir Mauhin3, Agnès Boullier4,5
1Department of Metabolic Biochemistry, Normandie University, UNIROUEN, INSERM U1245, CHU Rouen, 76000 Rouen, France.
Journal of Personalized Medicine
|September 28, 2021
Summary
Fabry disease (FD) shows significant metabolic remodeling, with 86 differentially expressed metabolites identified. Omics approaches reveal distinct metabolic profiles, aiding in understanding this complex lysosomal disorder.
Area of Science:
- Biochemistry
- Genetics
- Systems Biology
Background:
- Fabry disease (FD) is an X-linked lysosomal disorder caused by deficient alpha-galactosidase A (GalA) activity.
- FD presents complex genotype-phenotype correlations, affecting multiple organs and reducing life expectancy.
- Omics technologies offer a systems-level approach to explore FD's complexity.
Purpose of the Study:
- To identify metabolic profiles distinguishing FD patients from healthy controls.
- To explore the utility of metabolomics in understanding FD pathophysiology.
- To develop a predictive model for FD using identified metabolites.
Main Methods:
- Targeted metabolomics analysis of 188 metabolites in 66 FD patient plasmas and 60 controls using liquid chromatography-mass spectrometry.
- Determination of LysoGb3 concentration and GalA enzymatic activity.
- Application of univariate, systems biology, and machine learning analyses.
Main Results:
- Identification of 86 differentially expressed metabolites, including glycerophospholipids, acylcarnitines, sphingomyelins, amino acids, and biogenic amines.
- Network-based analysis revealed 13 consensus metabolites.
- A predictive model achieved an AUC-ROC of 0.992, demonstrating high accuracy in distinguishing FD patients.
Conclusions:
- FD exhibits profound metabolic alterations.
- Omics-based strategies are valuable for uncovering clinical and biological associations in lysosomal diseases.
- These findings support the generation of new pathophysiological hypotheses for FD.
