Abstract
Background
Sanfilippo disease (Mucopolysaccharidosis III) is a neurodegenerative lysosomal disorder characterized by accumulation of the glycosaminoglycan heparan sulfate (HS). MPS III has a large phenotypic variability and early assessment of disease severity is difficult. We investigated the correlation between disease severity and the plasma concentration of HS (pHS, defined by the sum of the heparan sulfate derived disaccharides obtained after enzymatic digestion) and urinary total GAGs level (uGAGs, measured by the dimethylene blue test) in a cross-sectional cohort of 44 MPS III patients.
Methods
Disease severity was established on the basis of the age of complete loss of independent walking and of full loss of speech in all patients. Hazard ratios (HR) were obtained with cox-regression analysis. In order to allow prediction of a severe phenotype based on a cut-off value for pHS, patients were divided in two groups (severely affected and less severely affected) based on predictive mutations or on the age of full loss of speech. Receiver operator characteristics (ROC) were obtained for pHS.
Results
pHS and uGAGs were independently and linearly associated with an increased risk of speech loss with a HR of 1.8 (95 % CI 1.3–2.7) per 500 ng/ml increase of HS in plasma (p = 0.002), and a HR of 2.7 (95 % CI 1.6–4.4) per 10 mg/mmol creatinine increase of uGAGs (p < 0.001). pHS and uGAGS were less strongly associated with loss of walking. The area under the ROC curve for pHS was 0.85, indicating good discrimination.
Conclusion
pHS and uGAGs may be useful biomarkers for prediction of severity in MPS III.
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Communicated by: Ed Wraith
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de Ruijter, J., IJlst, L., Kulik, W. et al. Heparan sulfate derived disaccharides in plasma and total urinary excretion of glycosaminoglycans correlate with disease severity in Sanfilippo disease. J Inherit Metab Dis 36, 271–279 (2013). https://doi.org/10.1007/s10545-012-9535-5
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DOI: https://doi.org/10.1007/s10545-012-9535-5