title: Cholestane-3β,5α,6β-triol: high levels in Niemann-Pick type C, cerebrotendinous xanthomatosis, and lysosomal acid lipase deficiency.
abstract: Niemann-Pick type C (NPC) is a progressive neurodegenerative disease characterized by lysosomal/endosomal accumulation of unesterified cholesterol and glycolipids. Recent studies have shown that plasma cholestane-3β,5α,6β-triol (CT) and 7-ketocholesterol (7-KC) could be potential biomarkers for the diagnosis of NPC patients. We aimed to know the sensitivity and specificity of these biomarkers for the diagnosis of NPC compared with other diseases that can potentially lead to oxysterol alterations. We studied 107 controls and 122 patients including 16 with NPC, 3 with lysosomal acid lipase (LAL) deficiency, 8 with other lysosomal diseases, 5 with galactosemia, 11 with cerebrotendinous xanthomatosis (CTX), 3 with Smith-Lemli-Opitz, 14 with peroxisomal biogenesis disorders, 19 with unspecific hepatic diseases, 13 with familial hypercholesterolemia, and 30 with neurological involvement and no evidence of an inherited metabolic disease. CT and 7-KC were analyzed by HPLC-ESI-MS/MS as mono-dimethylglycine derivatives. Levels of 7-KC were high in most of the studied diseases, whereas those of CT were only high in NPC, LAL, and CTX patients. Consequently, although CT is a sensitive biomarker of NPC disease, including those cases with doubtful filipin staining, it is not specific. 7-KC is a very unspecific biomarker.
authors.affiliation: Sección de Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), and Ciber Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pajares
authors.affiliation: Sección de Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), and Ciber Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Arias
authors.affiliation: Sección de Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), and Ciber Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: García-Villoria
authors.affiliation: Sección de Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), and Ciber Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Macías-Vidal
authors.affiliation: Lipid Clinic, Endocrinology and Nutrition Service, IDIBAPS, and Ciber Fisiopatología de la Obesidad y Nutrición (CIBEROBN) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.affiliation: Division of Pediatric Metabolism, Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: de las Heras
authors.affiliation: Sección de Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), and Ciber Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Girós
authors.affiliation: Sección de Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), and Ciber Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Coll
authors.affiliation: Sección de Errores Congénitos del Metabolismo, Servicio de Bioquímica y Genética Molecular, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), and Ciber Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Hospital Clinic, Barcelona, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002777:Cholestanols / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007653:Ketocholesterols / Q000097:blood*; D008297:Male; D008875:Middle Aged; D052556:Niemann-Pick Disease, Type C / Q000097:blood*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D015223:Wolman Disease / Q000097:blood* / Q000175:diagnosis; D019294:Xanthomatosis, Cerebrotendinous / Q000097:blood* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D002777:Cholestanols; D007653:Ketocholesterols; C000474:cholestane-3,5,6-triol; C003001:7-ketocholesterol
keywords: 3α,7α,12α-trihydroxycoprostane; 7-ketocholesterol; high-performance liquid chromatography/electrospray ionization/tandem mass spectrometry; oxysterols