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
  • 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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