{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:03:41Z","timestamp":1791147821980,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T00:00:00Z","timestamp":1347408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010sectional cohort of 44 MPS III patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010regression analysis. In order to allow prediction of a severe phenotype based on a cut\u2010off 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u20132.7) per 500 ng\/ml increase of HS in plasma (<jats:italic>p<\/jats:italic>\u2009=\u20090.002), and a HR of 2.7 (95 % CI 1.6\u20134.4) per 10 mg\/mmol creatinine increase of uGAGs (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>pHS and uGAGs may be useful biomarkers for prediction of severity in MPS III.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-012-9535-5","type":"journal-article","created":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T01:05:45Z","timestamp":1347411945000},"page":"271-279","source":"Crossref","is-referenced-by-count":20,"title":["Heparan sulfate derived disaccharides in plasma and total urinary excretion of glycosaminoglycans correlate with disease severity in Sanfilippo disease"],"prefix":"10.1002","volume":"36","author":[{"given":"J.","family":"de Ruijter","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Amsterdam Lysosome Centre \u2018Sphinx\u2019 University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"IJlst","sequence":"additional","affiliation":[{"name":"Lab. Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Kulik","sequence":"additional","affiliation":[{"name":"Lab. Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"van Lenthe","sequence":"additional","affiliation":[{"name":"Lab. Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Wagemans","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Amsterdam Lysosome Centre \u2018Sphinx\u2019 University of Amsterdam Amsterdam The Netherlands"},{"name":"Lab. Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"van Vlies","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Amsterdam Lysosome Centre \u2018Sphinx\u2019 University of Amsterdam Amsterdam The Netherlands"},{"name":"Lab. 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A.","family":"Wijburg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Amsterdam Lysosome Centre \u2018Sphinx\u2019 University of Amsterdam Amsterdam The Netherlands"},{"name":"Department of Pediatrics, Division of Metabolic Diseases (H7\u2010270) Academic Medical Centre (AMC) Meibergdreef 9 Amsterdam 1105 AZ The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0112-z"},{"key":"e_1_2_6_3_1","first-page":"782","article-title":"Incidence of mucopolysaccharidoses in Tunisia","volume":"87","author":"Ben Turkia H","year":"2009","journal-title":"Tunis 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