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

• Published in: FEBS letters Vol. 590; no. 11; pp. 1651 - 1662
• Main Authors: Mazzacuva, Francesca, Mills, Philippa, Mills, Kevin, Camuzeaux, Stephane, Gissen, Paul, Nicoli, Elena‐Raluca, Wassif, Christopher, Vruchte, Danielle, Porter, Forbes D., Maekawa, Masamitsu, Mano, Nariyasu, Iida, Takashi, Platt, Frances, Clayton, Peter T.
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01-06-2016
• Subjects: Adolescent; Adult; bile acids; Bile Acids and Salts - blood; Bile Acids and Salts - isolation & purification; Biomarkers; Biomarkers - blood; Blood Chemical Analysis - methods; Case-Control Studies; Child; Child, Preschool; Chromatography, High Pressure Liquid - methods; Early Diagnosis; GlcNAc transferase; Humans; Infant; Middle Aged; Niemann-Pick Disease, Type C - blood; Niemann-Pick Disease, Type C - diagnosis; Niemann‐Pick C; Research Letter; Research Letters; screening; Tandem Mass Spectrometry - methods; UPLC‐MS/MS; Young Adult; Biomarkers; UPLC-MS/MS; screening; Niemann-Pick C; bile acids; GlcNAc transferase
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.12196

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.