Identification of a serum biomarker for mucopolysaccharidosis I

The mucopolysaccharidoses are a clinically heterogeneous group of lysosomal storage disorders presenting with broad multi-system disease and a continuous range of phenotypes. Currently there are no objective biomarkers of MPS disease that clearly reflect disease severity or therapeutic responsiveness. Using proteomic studies in the murine MPS I model, I have identified the formation of the heparin cofactor II-thrombin (HCII-T) complex, a well-known serine protease inhibitor (serpin)-serine protease complex, as an informative biomarker for MPS I. MPS I patients showed a range of serum HCII-T concentrations from 16,300 - 208,600 pM, whereas the control values varied from 38.94 - 1491 pM. HCII-T complex was also elevated in plasma from MPS I patients and mice. The degree of HCII-T complex formation appears to correlate with disease severity and is responsive to therapy. In addition to its role as a biomarker, the discovery of increased serpin-serine protease complex formation provides a valuable insight into possible pathophysiological mechanisms of MPS disease.Medicine, Faculty ofMedical Genetics, Department ofGraduat