Heparin cofactor II-thrombin complex: a biomarker of MPS disease.
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.
Randall
Derrick R
DR
Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Room C234, Vancouver, BC, Canada V6H3N1.
Colobong
Karen E
KE
Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Room C234, Vancouver, BC, Canada V6H3N1.
Hemmelgarn
Harmony
H
Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Room C234, Vancouver, BC, Canada V6H3N1.
Sinclair
Graham B
GB
Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Room C234, Vancouver, BC, Canada V6H3N1.
Hetty
Elly
E
Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Room C234, Vancouver, BC, Canada V6H3N1.
Thomas
Anita
A
Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Room C234, Vancouver, BC, Canada V6H3N1.
Bodamer
Olaf A
OA
Department of Pediatrics, University Hospital Vienna, Austria.
Volkmar
Barbara
B
Department of Pediatrics, Paracelsus Medical School Salzburg, Austria.
Fernhoff
Paul M
PM
Department of Human Genetics, Emory University School of Medicine, Decatur, GA, USA.
Casey
Robin
R
Department of Medical Genetics, University of Calgary, Calgary, Alta., Canada.
Chan
Alicia K
AK
Department of Medical Genetics, University of Alberta, Edmonton, Alta., Canada.
Mitchell
Grant
G
Department of Pediatrics, Université de Montréal, Montréal, Que., Canada.
Stockler
Silvia
S
Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Melancon
Serge
S
Department of Pediatrics, McGill University, Montreal, Que., Canada.
Rupar
Tony
T
Department of Biochemistry and Paediatrics, University of Western Ontario, Ont., Canada.
Clarke
Lorne A
LA
Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Room C234, Vancouver, BC, Canada V6H3N1.
D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001774:Blood Chemical Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015844:Heparin Cofactor II / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D009083:Mucopolysaccharidoses / Q000097:blood* / Q000628:therapy; D013917:Thrombin / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; D015844:Heparin Cofactor II; D013917:Thrombin