Molecular genetics and metabolism. 2010;99(3):269-74.
Mucopolysaccharide (MPS) diseases are lysosomal storage disorders caused by deficiencies
of enzymes catabolising glycosaminoglycans (GAGs). Abnormal GAG accumulation leads
to symptoms including severe progressive neurological decline, skeletal deformities,
organomegally, respiratory compromise and premature death. Treatment is available
for some MPS diseases; enzyme replacement therapy for MPS I, II and VI, and haematopoietic
stem cell transplantation for MPS I, VI and VII. These treatments are reliant on early
diagnosis of the disease and accurate monitoring of treatment outcomes. Blood enzyme
levels and total urinary GAGs are commonly used biomarkers in diagnosis of MPS but
are not good measures of treatment outcome. Serum heparin cofactor II-thrombin complex
(HCII-T), which is a GAG regulated serpin-protease complex, has recently been identified
as a promising biomarker for MPS diseases. Here we present an assessment of the HCII-T
biomarker in mouse models of MPS I, IIIA and IIIB, which suggests that HCII-T is a
reliable marker for MPS I when measured in serum or dried blood spots stored for over
a year at 4 degrees C, but that murine MPS IIIA and IIIB cannot be reliably detected
using this biomarker. We also show that HCII-T formation in vivo is dependent on the
presence of excess intravenous dermatan sulphate (DS), whilst intravenous heparan
sulphate (HS), does not promote complex formation effectively. This suggests that
HCII-T will prove effective as a biomarker for MPS I, II, VI and VII diseases, storing
dermatan sulphate but may not be as appropriate for MPS III, storing heparan sulphate.
With careful sample preparation, HCII-T ELISA could prove to be a useful biomarker
for both newborn screening and measurement of treatment outcomes in selected MPS diseases.