Unit

UNIT 17.12 Quantification of Glycosaminoglycans in Urine by Isotope-Dilution Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry

  1. Haoyue Zhang,
  2. Sarah P. Young,
  3. David S. Millington

Published Online: 1 JAN 2013

DOI: 10.1002/0471142905.hg1712s76

Current Protocols in Human Genetics

Current Protocols in Human Genetics

How to Cite

Zhang, H., Young, S. P. and Millington, D. S. 2013. Quantification of Glycosaminoglycans in Urine by Isotope-Dilution Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry. Current Protocols in Human Genetics. 76:17.12:17.12.1–17.12.14.

Author Information

  1. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina

Publication History

  1. Published Online: 1 JAN 2013

Abstract

Mucopolysaccharidoses (MPSs) are complex lysosomal storage disorders that result in the accumulation of glycosaminoglycans (GAGs) in urine, blood, and tissues. Lysosomal enzymes responsible for GAG degradation are defective in MPSs. GAGs including chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS) are disease-specific biomarkers for MPSs. This unit describes a stable isotope dilution-tandem mass spectrometric method for quantifying CS, DS, and HS in urine samples. The GAGs are methanolyzed to uronic or iduronic acid-N-acetylhexosamine or iduronic acid-N-sulfo-glucosamine dimers and mixed with internal standards derived from deuteriomethanolysis of GAG standards. Specific dimers derived from HS, DS, and CS are separated by ultra-performance liquid chromatography (UPLC) and analyzed by electrospray ionization tandem mass spectrometry (MS/MS) using selected reaction monitoring for each targeted GAG product and its corresponding internal standard. This new GAG assay is useful for identifying patients with MPS types I, II, III, VI, and VII. Curr. Protoc. Hum. Genet. 76:17.12.1-17.12.14. © 2013 by John Wiley & Sons, Inc.

Keywords:

  • glycosaminoglycans;
  • dermatan sulfate;
  • heparan sulfate;
  • mucopolysaccharidosis;
  • LC-ESI-MS/MS