title: Identification of novel bile acids as biomarkers for the early diagnosis of Niemann-Pick C disease.
abstract: This article describes a rapid UPLC-MS/MS method to quantitate novel bile acids in biological fluids and the evaluation of their diagnostic potential in Niemann-Pick C (NPC). Two new compounds, NPCBA1 (3β-hydroxy,7β-N-acetylglucosaminyl-5-cholenoic acid) and NPCBA2 (probably 3β,5α,6β-trihydroxycholanoyl-glycine), were observed to accumulate preferentially in NPC patients: median plasma concentrations of NPCBA1 and NPCBA2 were 40- and 10-fold higher in patients than in controls. However, NPCBA1 concentrations were normal in some patients because they carried a common mutation inactivating the GlcNAc transferase required for the synthesis of this bile acid. NPCBA2, not containing a GlcNAc moiety, is thus a better NPC biomarker.
authors.affiliation: Centre for Translational Omics, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mazzacuva
authors.affiliation: Centre for Translational Omics, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.
authors.forename: Philippa
authors.initials: P
authors.lastname: Mills
authors.affiliation: Centre for Translational Omics, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Mills
authors.affiliation: Centre for Translational Omics, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.
authors.forename: Stephane
authors.initials: S
authors.lastname: Camuzeaux
authors.affiliation: Centre for Translational Omics, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.|Metabolic Medicine, Great Ormond Street Children's Hospital, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Gissen
authors.affiliation: Department of Pharmacology, University of Oxford, UK.
authors.forename: Elena-Raluca
authors.initials: ER
authors.lastname: Nicoli
authors.affiliation: Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wassif
authors.affiliation: Department of Pharmacology, University of Oxford, UK.
authors.forename: Danielle
authors.initials: D
authors.lastname: Te Vruchte
authors.affiliation: Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Maekawa
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital, Japan.
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
authors.affiliation: College of Humanities and Sciences, Nihon University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
authors.affiliation: Department of Pharmacology, University of Oxford, UK.
authors.forename: Frances
authors.initials: F
authors.lastname: Platt
authors.affiliation: Centre for Translational Omics, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.|Metabolic Medicine, Great Ormond Street Children's Hospital, London, UK.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Clayton
mesh_terms: D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood* / Q000302:isolation & purification; D015415:Biomarkers / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D042241:Early Diagnosis; D006801:Humans; D007223:Infant; D008875:Middle Aged; D052556:Niemann-Pick Disease, Type C / Q000097:blood* / Q000175:diagnosis*; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers
keywords: Biomarkers; GlcNAc transferase; Niemann-Pick C; UPLC-MS/MS; bile acids; screening