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. 2018 Sep;125(1-2):44-52.
doi: 10.1016/j.ymgme.2018.04.011. Epub 2018 May 17.

Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis

Shaukat A Khan  1 , Robert W Mason  1 , Roberto Giugliani  2 , Kenji Orii  3 , Toshiyuki Fukao  3 , Yasuyuki Suzuki  4 , Seiji Yamaguchi  5 , Hironori Kobayashi  5 , Tadao Orii  3 , Shunji Tomatsu  6
Affiliations

Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis

Shaukat A Khan et al. Mol Genet Metab. 2018 Sep.

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.

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Conflict of interest statement

Conflict of interest

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

Figure 1
Figure 1
Age-dependent DS (A), diHS-NS (B), diHS-0S (C), mono-sulfated KS (D), di- sulfated KS (E) and % of di-sulfated KS in total KS, in the urine of untreated or ERT MPS IVA, untreated MPS IVB, and untreated or ERT MPS VI patients.
Figure 2
Figure 2
Pearson’s correlation between plasma and urine mono-sulfated KS of treated and untreated MPS IVA patients (A), correlation between plasma and urine di-sulfated KS of treated and untreated MPS IVA patients (B).
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