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Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses

Nemours/Alfred I duPont Hospital for Children, Wilmington, DE 19803, USA
Department of Pediatrics, Saint Louis University, St. Louis, MO 63104, USA
Agilent Technologies, Inc., Wakefield, MA 01880, USA
Department of Genetics/UFRGS, Medical Genetics Service/HCPA, Porto Alegre 90035-903, Brazil
Department of Pediatrics, Shimane University, Shimane 693-8501, Japan
Medical Education Development Center, Gifu University, Gifu 501-1194, Japan
Department of Pediatrics, Gifu University, Gifu 501-1194, Japan
Author to whom correspondence should be addressed.
Metabolites 2014, 4(3), 655-679;
Received: 18 June 2014 / Revised: 26 July 2014 / Accepted: 28 July 2014 / Published: 11 August 2014
(This article belongs to the Special Issue Inborn Errors of Metabolism)
Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs. View Full-Text
Keywords: mucopolysaccharidoses; ELISA; tandem mass spectrometry; glycosaminoglycan; chondroitin sulfate; dermatan sulfate; heparan sulfate; keratan sulfate mucopolysaccharidoses; ELISA; tandem mass spectrometry; glycosaminoglycan; chondroitin sulfate; dermatan sulfate; heparan sulfate; keratan sulfate
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Tomatsu, S.; Shimada, T.; Mason, R.W.; Montaño, A.M.; Kelly, J.; LaMarr, W.A.; Kubaski, F.; Giugliani, R.; Guha, A.; Yasuda, E.; Mackenzie, W.; Yamaguchi, S.; Suzuki, Y.; Orii, T. Establishment of Glycosaminoglycan Assays for Mucopolysaccharidoses. Metabolites 2014, 4, 655-679.

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