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. 2025 Mar 1;21(2):35.
doi: 10.1007/s11306-025-02233-3.

Identification of gangliosides and ceramides as biomarkers for mucopolysaccharidosis type II (hunter syndrome) through untargeted lipidomic analysis

Asma Farjallah  1 , Bruno Maranda  1 , Roberto Giugliani  2 , Christiane Auray-Blais  3
Affiliations

Identification of gangliosides and ceramides as biomarkers for mucopolysaccharidosis type II (hunter syndrome) through untargeted lipidomic analysis

Asma Farjallah et al. Metabolomics. .

Abstract

Introduction: Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked recessive disorder caused by iduronate-2-sulfatase deficiency, affecting mainly male patients. The lack of its enzyme activity causes the accumulation of the glycosaminoglycans heparan sulfate and dermatan sulfate in all body tissues and leads to a secondary accumulation of gangliosides and ceramides.

Objective and methods: We conducted a lipidomic study to investigate the dysregulation of lipid pathways in neuronopathic MPS type II. A modified liquid extraction was performed for untargeted lipid analysis. A reverse phase ultraperformance liquid chromatography coupled to quadrupole time-of-flight (UPLC-QTOF) mass spectrometry allowed the identification of upregulated ganglioside and ceramide biomarkers in the plasma and urine of a MPS II patient group compared to a healthy control group.

Results: The altered pathways, including those related to glycerophospholipid metabolism and fatty acid oxidation, highlight the essential role of lipid metabolism in the progression of the disease.

Conclusion: The accumulation of gangliosides and ceramides could be associated with the neuropathology in various lysosomal storage diseases including MPS II.

Keywords: Lipids; Lysosomal storage disease; Mass spectrometry; Neurodegeneration.

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Conflict of interest statement

Declarations. Conflict of interest: (A) Farjallah has received a research salary for her work during this project. C. Auray-Blais has received grants from Takeda Pharmaceutical International AG, as well as honoraria for lectures given from Sanofi Genzyme, BioMarin Pharmaceuticals Inc., Protalix Biotherapeutics, Amicus Therapeutics, Avrobio, and traveling expenses from Waters Corp. for lectures given. She has received service agreements from Moderna Therapeutics, Sigilon Therapeutics, and 4D Molecular Therapeutics. R. Giugliani received investigator grant, and/or consulting fees and/or speaker honoraria from Alexion, Allievex, Alnylam, Amicus, Astellas, Azafaros, BioMarin, Chiesi, Cyclo, JCR, Novartis, Paradigm, PassageBio, Pfizer, PTC, RegenxBio, Sanofi, Takeda and Ultragenyx. (B) Maranda is the medical director at MendeliKABS Inc.

References

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