Urine keratan sulfate (uKS) elevation in lysosomal disorders (LSD): Comparison of uKS levels in Morquio/MPS IV versus non-Morquio LSD
| Autor: | Tim Wood, Haoyue Zhang, Frits A. Wijburg, Paul Harmatz, Nicole Miller, Pamela Lavoie, Roberto Giugliani, Christiane Auray-Blais, Naomi van Vlies, Katarzyna Ellsworth, David S. Millington |
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| Rok vydání: | 2015 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Chromatography Keratan sulfate Endocrinology Diabetes and Metabolism nutritional and metabolic diseases Urine Heparan sulfate Biochemistry High-performance liquid chromatography Dermatan sulfate Excretion Glycosaminoglycan chemistry.chemical_compound Endocrinology chemistry Liquid chromatography–mass spectrometry Genetics skin and connective tissue diseases Molecular Biology |
| Zdroj: | Molecular Genetics and Metabolism. 114:S16 |
| ISSN: | 1096-7192 |
| Popis: | CO RR EC TE D P RO OF patients affected with different types of MPS, such as Hurler, Hurler/ Scheie and Scheie (MPS I/H, IH/S, I/S), Hunter (MPS II), Sanfilippo (MPS III), Morquio (MPS IV) and Maroteaux–Lamy (MPS VI) syndromes. Therefore, we have developed a quantitative methodology for the analysis of urine samples using an ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) multiplex approach. Specific glycosaminoglycans such as dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS) were specifically targeted for mass spectrometry analysis. Twenty-five microliters of urine was evaporated at room temperature under a nitrogen flow. A methanolysis reaction was performed by adding methanol–HCl·3N to the dried urine sample, followed by heating at 65 °C for 60 min. After a second nitrogen evaporation, the residue was suspended in 200 μl of a solution containing deuterated internal standards synthesized in-house. Two microliters were injected onto an Acquity I-Class UPLC coupled to a Xevo TQ-S mass spectrometry system (Waters Corp.). The high sensitivity and good resolution of this methodology allowed the detection of small quantities of urinary GAG. Urinary excretion of specific GAG permitted a good differentiation between patients with MPS I, II, III, IV and VI and healthy reference controls. Except for MPS I and II which are characterized by the same GAG excretion profile, each MPS type was distinguished from one another due to a specific GAG profile. This UPLC–MS/MS quantitation of dermatan sulfate, heparan sulfate, and keratan sulfate is specific and sensitive for the detection of MPS disorders. This methodology might be applicable to high-risk screening and reliable for the diagnosis, and monitoring of treated MPS patients. |
| Databáze: | OpenAIRE |
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