Identification of novel bile acids as biomarkers for the early diagnosis of Niemann‐Pick C disease. Issue 11 (27th May 2016)

• Record Type: Journal Article
• Authors: Mazzacuva, Francesca; Mills, Philippa; Mills, Kevin; Camuzeaux, Stephane; Gissen, Paul; Nicoli, Elena‐Raluca; Wassif, Christopher; te Vruchte, Danielle; Porter, Forbes D.; Maekawa, Masamitsu; Mano, Nariyasu; Iida, Takashi; Platt, Frances; Clayton, Peter T.
• Is Part Of: FEBS letters. Volume 590:Issue 11(2016)
• Page Start: 1651
• Page End: 1662
• Publication Date: 2016-05-27
• Subjects: bile acids -- Biomarkers -- GlcNAc transferase -- Niemann‐Pick C -- screening -- UPLC‐MS/MS; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12196
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract :