Heparin cofactor II-thrombin complex: A biomarker of MPS disease

Derrick R. Randall, Karen E. Colobong, Harmony Hemmelgarn, Graham B. Sinclair, Elly Hetty, Anita Thomas, Olaf A. Bodamer, Barbara Volkmar, Paul M. Fernhoff, Robin Casey, Alicia K. Chan, Grant Mitchell, Silvia Stockler, Serge Melancon, Tony Rupar, Lorne A. Clarke

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


The mucopolysaccharidoses are a group of lysosomal storage disorders caused by defects in the degradation of glycosaminoglycans. Each disorder is characterized by progressive multi-system disease with considerable clinical heterogeneity. The clinical heterogeneity of these disorders is thought to be related to the degree of the metabolic block in glycosaminoglycan degradation which in turn is related to the underlying mutation at the respective locus. There are currently no objective means other than longitudinal clinical observation, or the detection of a recurrent genetic mutation to accurately predict the clinical course for an individual patient, particularly when diagnosed early. In addition, there are no specific disease biomarkers that reflect the total body burden of disease. The lack of specific biomarkers has made monitoring treatment responses and predicting disease course difficult in these disorders. The recent introduction of enzyme replacement therapy for MPS I, II, and VI highlights the need for objective measures of disease burden and disease responsiveness. We show that serum levels of heparin cofactor II-thrombin complex is a reliable biomarker of the mucopolysaccharidoses. Untreated patients have serum levels that range from 3- to 112-fold above control values. In a series of patients with varying severity of mucopolysaccharidosis I, the serum complex concentration was reflective of disease severity. In addition, serum heparin cofactor II-thrombin levels showed responsiveness to various treatment regimens. We propose that serum levels of heparin cofactor II-thrombin complex may provide an important assessment and monitoring tool for patients with mucopolysaccharidosis.

Original languageEnglish (US)
Pages (from-to)456-461
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number4
StatePublished - Aug 2008
Externally publishedYes


  • Biomarker
  • Enzyme replacement therapy
  • Glycosaminoglycan
  • Heparin cofactor II
  • Lysosomal storage disease
  • Lysosome
  • Mucopolysaccharidosis
  • Thrombin

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism


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