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01-03-2013 | Original Article

Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long-term enzyme replacement therapy (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans

Authors: Minke H. de Ru, Linda van der Tol, Naomi van Vlies, Brian W. Bigger, Carla E. M. Hollak, Lodewijk IJlst, Wim Kulik, Henk van Lenthe, Muhammad A. Saif, Tom Wagemans, Willem M. van der Wal, Ronald J. Wanders, Frits A. Wijburg

Published in: Journal of Inherited Metabolic Disease | Issue 2/2013

Abstract

Introduction

Mucopolysaccharidosis type I (MPS I) results in a defective breakdown of the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate, which leads to a progressive disease. Enzyme replacement therapy (ERT) results in clearance of these GAGs from a range of tissues and can significantly ameliorate several symptoms. The biochemical efficacy of ERT is generally assessed by the determination of the total urinary excretion of GAGs. However, this has limitations. We studied the concentrations of heparan sulfate and dermatan sulfate derived disaccharides (HS and DS, respectively) in the plasma and urine of seven patients and compared these levels with total urinary GAGs (uGAGs) levels.

Methods

Plasma and urine samples were collected at different time points relative to the weekly ERT for three non-consecutive weeks in seven MPS I patients who had been treated with ERT for at least 2.5 years. Heparan and dermatan sulfate in plasma and urine were enzymatically digested into disaccharides, and HS and DS levels were determined by HPLC-MS/MS analysis. uGAGs were measured by the DMB test.

Results

The levels of HS and DS were markedly decreased compared with the levels before the initiation of ERT. However, the concentrations of DS in plasma and of both HS and DS in urine remained significantly elevated in all studied patients, while in six patients the level of total uGAGs had normalized. The concentrations of plasma and urinary HS during the weekly ERT followed a U-shaped curve. However, the effect size is small. The concentrations of plasma and urinary DS and uGAGs appeared to be in a steady state.

Conclusions

HS and DS are sensitive biomarkers for monitoring the biochemical treatment efficacy of ERT and remain elevated despite long-term treatment. This finding may be related to the labeled dose or antibody status of the patient. The timing of the sample collection is not relevant, at least at the current dose of 100 IU/kg/weekly.

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Title: Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long-term enzyme replacement therapy (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans
Authors: Minke H. de Ru
Linda van der Tol
Naomi van Vlies
Brian W. Bigger
Carla E. M. Hollak
Lodewijk IJlst
Wim Kulik
Henk van Lenthe
Muhammad A. Saif
Tom Wagemans
Willem M. van der Wal
Ronald J. Wanders
Frits A. Wijburg
Publication date: 01-03-2013
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 2/2013
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-012-9538-2

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