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Longitudinal observations of serum heparin cofactor II-thrombin complex in treated Mucopolysaccharidosis I and II patients

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Journal of Inherited Metabolic Disease

Abstract

Monitoring of therapeutic response in mucopolysaccharidosis (MPS) patients is problematic as most biomarkers are specific for either disease complications or specific organ system involvement. Recent studies have indicated that serum heparin-cofactor II-thrombin complex (HCII-T) may serve as an important biomarker in the group of MPSs where dermatan sulphate is stored. This complex forms when blood coagulates in the presence of glycosaminoglycans (GAGs) where the ultimate amount of HCII-T that forms reflects the concentration of circulating GAGs. We have studied serum HCII-T levels in 9 MPS I and 11 MPS II treated patients and have compared values to studies of urinary GAGs. In severe MPS I patients treated with either transplantation or enzyme replacement therapy (ERT), serum HCII-T levels never reach the range of normal despite normalization of uGAGs in some patients. Some attenuated MPS I patients have normalization of HCII-T but require a protracted exposure time relative to the drop in urinary GAGs. Treated MPS II patients show a clear correlation of serum HCII-T levels with the presence of antibodies to Idursulfase, with antibody positive patients showing an early drop in HCII-T levels with eventual increases in levels often to levels above those seen at baseline. This is contrasted by a robust and persistent drop in uGAGs. Antibody negative MPS II patients show a drop in HCII-T levels on treatment but levels never normalize despite normalization of uGAGs. This study highlights the utility and biologic relevance of serum HCII-T levels in monitoring therapy in these disorders.

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Acknowledgment

This work was supported from a research grant awarded to LAC from the Canadian MPS Society. LAC hold a senior investigatorship through the Child and Family Research Institute. This paper is dedicated to the loving memory of Karen Colobong, our friend, colleague and dedicated researcher.

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Correspondence to Lorne Andrew Clarke.

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Communicated by: Olaf Bodamer

Competing interest: None declared.

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Clarke, L.A., Hemmelgarn, H., Colobong, K. et al. Longitudinal observations of serum heparin cofactor II-thrombin complex in treated Mucopolysaccharidosis I and II patients. J Inherit Metab Dis 35, 355–362 (2012). https://doi.org/10.1007/s10545-011-9369-6

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  • DOI: https://doi.org/10.1007/s10545-011-9369-6

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