Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis
- PMID: 29779903
- PMCID: PMC6175648
- DOI: 10.1016/j.ymgme.2018.04.011
Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis
Abstract
To explore the correlation between glycosaminoglycan (GAG) levels and mucopolysaccharidosis (MPS) type, we have evaluated the GAG levels in blood of MPS II, III, IVA, and IVB and urine of MPS IVA, IVB, and VI by tandem mass spectrometry. Dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS; mono-sulfated KS, di-sulfated KS), and the ratio of di-sulfated KS in total KS were measured. Patients with untreated MPS II had higher levels of DS and HS in blood while untreated MPS III had higher levels of HS in blood than age-matched controls. Untreated MPS IVA had higher levels of KS in blood and urine than age-matched controls. The ratio of blood di-sulfated KS/total KS in untreated MPS IVA was constant and higher than that in controls for children up to 10 years of age. The ratio of urine di-sulfated KS/total KS in untreated MPS IVA was also higher than that in age-matched controls, but the ratio in untreated MPS IVB was lower than controls. ERT reduced blood DS and HS in MPS II, and urine KS in MPS IVA patients, although GAGs levels remained higher than the observed in age-matched controls. ERT did not change blood KS levels in MPS IVA. MPS VI under ERT still had an elevation of urine DS level compared to age-matched controls. There was a positive correlation between blood and urine KS in untreated MPS IVA patients but not in MPS IVA patients treated with ERT. Blood and urine KS levels were secondarily elevated in MPS II and VI, respectively. Overall, measurement of GAG levels in blood and urine is useful for diagnosis of MPS, while urine KS is not a useful biomarker for monitoring therapeutic efficacy in MPS IVA.
Keywords: Chondroitin sulfate; Dermatan sulfate; Glycosaminoglycans; Heparan sulfate; Hyaluronan; Keratan sulfate; LC/MS; Mucopolysaccharidoses.
Copyright © 2018 Elsevier Inc. All rights reserved.
Conflict of interest statement
All the authors contributed to this Article and had no conflict of interest with any other party. Shaukat A Khan, Robert W. Mason, Roberto Giugliani, Kenji Orii, Toshiyuki Fukao, Seiji Yamaguchi, Hironori Kobayashi, Tadao Orii, and Shunji Tomatsu declare that they have no conflict of interests.
Figures


References
-
- Neufeld MJ. The Metabolic and Molecular Bases of Inherited Disease. In: Scriver CBASWVD, editor. The mucopolysaccharidoses. McGraw-Hill; New York: 2001. pp. 3421–3452.
-
- Bjornsson S. Quantitation of proteoglycans as glycosaminoglycans in biological fluids using an alcian blue dot blot analysis. Analytical biochemistry. 1998;256:229–237. - PubMed
-
- de Jong JG, Hasselman JJ, van Landeghem AA, Vader HL, Wevers RA. The spot test is not a reliable screening procedure for mucopolysaccharidoses. Clinical chemistry. 1991;37:572–575. - PubMed
-
- de Jong JG, Wevers RA, Laarakkers C, Poorthuis BJ. Dimethylmethylene blue-based spectrophotometry of glycosaminoglycans in untreated urine: a rapid screening procedure for mucopolysaccharidoses. Clinical chemistry. 1989;35:1472–1477. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources