2. Academic Validation
  3. Identification of novel bile acids as biomarkers for the early diagnosis of Niemann-Pick C disease

Identification of novel bile acids as biomarkers for the early diagnosis of Niemann-Pick C disease

  • FEBS Lett. 2016 Jun;590(11):1651-62. doi: 10.1002/1873-3468.12196.
Francesca Mazzacuva 1,  Philippa Mills 1,  Kevin Mills 1,  Stephane Camuzeaux 1,  Paul Gissen 1 2,  Elena-Raluca Nicoli 3,  Christopher Wassif 4,  Danielle Te Vruchte 3,  Forbes D Porter 4,  Masamitsu Maekawa 5,  Nariyasu Mano 5,  Takashi Iida 6,  Frances Platt 3,  Peter T Clayton 1 2
Affiliations

Affiliations

  • 1 Centre for Translational Omics, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.
  • 2 Metabolic Medicine, Great Ormond Street Children's Hospital, London, UK.
  • 3 Department of Pharmacology, University of Oxford, UK.
  • 4 Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • 5 Department of Pharmaceutical Sciences, Tohoku University Hospital, Japan.
  • 6 College of Humanities and Sciences, Nihon University, Tokyo, Japan.
PMID: 27139891 DOI: 10.1002/1873-3468.12196
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.

Keywords

Biomarkers; GlcNAc transferase; Niemann-Pick C; UPLC-MS/MS; bile acids; screening.

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