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

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.