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

• Published in: Journal of inherited metabolic disease Vol. 36; no. 2; pp. 247 - 255
• Main Authors: de Ru, Minke H., van der Tol, Linda, van Vlies, Naomi, Bigger, Brian W., Hollak, Carla E. M., IJlst, Lodewijk, Kulik, Wim, van Lenthe, Henk, Saif, Muhammad A., Wagemans, Tom, van der Wal, Willem M., Wanders, Ronald J., Wijburg, Frits A.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2013; Blackwell Publishing Ltd
• Subjects: Adolescent; Adult; Aged; Biochemistry; Biomarkers - blood; Biomarkers - urine; Child; Child, Preschool; Dermatan Sulfate - blood; Dermatan Sulfate - metabolism; Dermatan Sulfate - urine; Disaccharides - blood; Disaccharides - metabolism; Disaccharides - urine; Enzyme Replacement Therapy; Female; Glycosaminoglycans - urine; Heparitin Sulfate - blood; Heparitin Sulfate - metabolism; Heparitin Sulfate - urine; Human Genetics; Humans; Infant; Infant, Newborn; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mucopolysaccharidosis I - blood; Mucopolysaccharidosis I - drug therapy; Mucopolysaccharidosis I - metabolism; Mucopolysaccharidosis I - urine; Original Article; Pediatrics; Young Adult; Heparan Sulfate; Enzyme Replacement Therapy; Label Dose; Disaccharide; Dermatan Sulfate
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-012-9538-2

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.