BACKGROUND: Alpha-mannosidosis is a rare lysosomal storage disorder caused by deficiency of the lysosomal enzyme alpha-mannosidase, which leads to the accumulation of mannose-rich oligosaccharides. Serum oligosaccharides are useful biomarkers for the therapeutic monitoring of patients with alpha-mannosidosis. In this study, we have developed a ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for thetrue quantitation of GlcNAc(Man) RESULTS: In plasma samples from 16 untreated alpha-mannosidosis patients, GlcNAc(Man) CONCLUSIONS: This study indicates that the analysis of serum/plasma oligosaccharides by UPLC-MS/MS is a feasible and valuable tool for diagnosis, and treatment monitoring of patients with alpha-mannosidosis.