{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:45:01Z","timestamp":1778633101553,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T00:00:00Z","timestamp":1511913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Niemann\u2010Pick type C (NP\u2010C), one of 50 inherited lysosomal storage disorders, is caused by NPC protein impairment that leads to unesterified cholesterol accumulation in late endosomal\/lysosomal compartments. The clinical manifestations of NP\u2010C include hepatosplenomegaly, neurological and psychiatric symptoms. Current diagnosis for NP\u2010C is based on observation of the accumulated cholesterol in fibroblasts of affected individuals, using an invasive and time expensive test, called Filipin staining. Lately, two metabolites that are markedly increased in NP\u2010C patients are arising as biomarkers for this disease screening: 7\u2010ketocholesterol and cholestane\u20103\u03b2,5\u03b1,6\u03b2\u2010triol, both oxidized cholesterol products.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>In this work, we aimed to evaluate the performance of cholestane\u20103\u03b2,5\u03b1,6\u03b2\u2010triol analysis for the screening and monitoring of NPC patients, correlating it with chitotriosidase levels, Filipin staining and molecular analysis. It was investigated 76 non\u2010treated individuals with NP\u2010C suspicion and also 7 patients with previous NP\u2010C diagnosis under treatment with miglustat, in order to verify the cholestane\u20103\u03b2,5\u03b1,6\u03b2\u2010triol value as a tool for therapy monitoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Considering molecular assay as golden standard, it was verified that cholestane\u20103\u03b2,5\u03b1,6\u03b2\u2010triol analysis presented 88% of sensitivity, 96.08% of specificity, a positive and negative predictive value calculated in 91.67% and 94.23%, respectively, for the diagnosis of NP\u2010C. Chitotriosidase levels were increased in patients with positive molecular analysis for NP\u2010C. For Filipin staining, it was found 1 false positive, 7 false negative and 24 inconclusive cases, showing that this assay has important limitations for NP\u2010C diagnosis. Besides, we found a significant decrease in cholestane\u20103\u03b2,5\u03b1,6\u03b2\u2010triol concentrations in NP\u2010C patients under therapy with miglustat when compared to non\u2010treated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Taken together, the present data show that cholestane\u20103\u03b2,5\u03b1,6\u03b2\u2010triol analysis has a high potential to be an important NP\u2010C screening assay, and also can be used for therapy monitorization with miglustat in NP\u2010C patients.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2017.11.007","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T22:02:04Z","timestamp":1511992924000},"page":"18-23","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Molecular and biochemical biomarkers for diagnosis and therapy monitorization of Niemann\u2010Pick type C patients"],"prefix":"10.1002","volume":"66","author":[{"given":"Tatiane Grazieli","family":"Hammerschmidt","sequence":"first","affiliation":[{"name":"Departamento de An\u00e1lises, Faculdade de Farm\u00e1cia UFRGS Avenida Ipiranga, 2752 CEP 90610\u2010000 Porto Alegre RS Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, UFRGS Av. 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