A multiplexed targeted method for profiling of serum gangliosides and glycosphingolipids: application to GM2-gangliosidosis
Document Type
Article
Publication Title
Analytical and Bioanalytical Chemistry
Abstract
The analysis of gangliosides and glycosphingolipids is crucial for understanding cellular membrane structure and function as well as to accurately diagnose certain inborn errors of metabolism. GM2-gangliosidosis represents a rare and fatal group of lysosomal storage disorders characterized by accumulation of GM2 gangliosides in various tissues and organs. These disorders arise due to deficiency or functional impairment of the β-hexosaminidase A or B enzymes, which are responsible for degradation of GM2 ganglioside. Deficient enzyme activity primarily leads to the accumulation of GM2 gangliosides within the lysosomes of cells. Accurate and rapid diagnostic methods that detect increased levels of GM2 gangliosides in patients with GM2-gangliosidosis can play a significant role in early diagnosis and appropriate treatment of this condition. To address this need, we developed a multiplexed liquid chromatography-tandem mass spectrometry method targeting 84 species of gangliosides and other glycosphingolipids involved in ganglioside metabolism. Reproducibility, linearity, extraction efficiency, and sample stability were evaluated and proof-of-concept data obtained from analysis of serum samples from confirmed cases of GM2-gangliosidosis. This method has the potential to simultaneously monitor the biosynthesis of gangliosides and the lysosomal catabolic pathway serving as a valuable tool for screening and diagnosing an important group of lysosomal storage disorders.
First Page
5689
Last Page
5699
DOI
10.1007/s00216-024-05487-3
Publication Date
11-1-2024
Recommended Citation
Kim, Jinyong; Byeon, Seul Kee; Oglesbee, Devin; and Schultz, Matthew J., "A multiplexed targeted method for profiling of serum gangliosides and glycosphingolipids: application to GM2-gangliosidosis" (2024). Open Access archive. 9906.
https://impressions.manipal.edu/open-access-archive/9906