Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Analysis of Urinary Oligosaccharides and Glycoamino Acids for the Diagnosis of Mucopolysaccharidosis and Glycoproteinosis
Issued Date
2024-06-01
Resource Type
ISSN
00099147
eISSN
15308561
Scopus ID
2-s2.0-85195178756
Pubmed ID
38597162
Journal Title
Clinical Chemistry
Volume
70
Issue
6
Start Page
865
End Page
877
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical Chemistry Vol.70 No.6 (2024) , 865-877
Suggested Citation
Wongkittichote P., Cho S.H., Miller A., King K., Herbst Z.M., Ren Z., Gelb M.H., Hong X. Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Analysis of Urinary Oligosaccharides and Glycoamino Acids for the Diagnosis of Mucopolysaccharidosis and Glycoproteinosis. Clinical Chemistry Vol.70 No.6 (2024) , 865-877. 877. doi:10.1093/clinchem/hvae043 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/98696
Title
Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Analysis of Urinary Oligosaccharides and Glycoamino Acids for the Diagnosis of Mucopolysaccharidosis and Glycoproteinosis
Corresponding Author(s)
Other Contributor(s)
Abstract
BACKGROUND: Mucopolysaccharidosis (MPS) and glycoproteinosis are 2 groups of heterogenous lysosomal storage disorders (LSDs) caused by defective degradation of glycosaminoglycans (GAGs) and glycoproteins, respectively. Oligosaccharides and glycoamino acids have been recognized as biomarkers for MPS and glycoproteinosis. Given that both groups of LSDs have overlapping clinical features, a multiplexed assay capable of unambiguous subtyping is desired for accurate diagnosis, and potentially for severity stratification and treatment monitoring. METHODS: Urinary oligosaccharides were derivatized with 3-methyl-1-phenyl-2-pyrazoline-5-one (PMP) and analyzed by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) together with the underivatized glycoamino acids. Novel biomarkers were identified with a semi-targeted approach with precursor mass scanning, the fragmentation pattern (if applicable), and the biochemical basis of the condition. RESULTS: A UPLC-MS/MS analysis with improved chromatographic separation was developed. Novel biomarkers for MPS-IIIA, IIIB, IIIC, and VII were identified and validated. A total of 28 oligosaccharides, 2 glycoamino acids, and 2 ratios were selected as key diagnostic biomarkers. Validation studies including linearity, lower limit of quantitation (LLOQ), and precision were carried out with the assay performance meeting the required criteria. Age-specific reference ranges were collected. In the 76 untreated patients, unambiguous diagnosis was achieved with 100% sensitivity and specificity. Additionally, the levels of disease-specific biomarkers were substantially reduced in the treated patients. CONCLUSIONS: A multiplexed UPLC-MS/MS assay for urinary oligosaccharides and glycoamino acids measurement was developed and validated. The assay is suitable for the accurate diagnosis and subtyping of MPS and glycoproteinosis, and potentially for severity stratification and monitoring response to treatment.