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Identification of novel bile acids as biomarkers for the early diagnosis of Niemann‐Pick C disease
Author(s) -
Mazzacuva Francesca,
Mills Philippa,
Mills Kevin,
Camuzeaux Stephane,
Gissen Paul,
Nicoli ElenaRaluca,
Wassif Christopher,
Vruchte Danielle,
Porter Forbes D.,
Maekawa Masamitsu,
Mano Nariyasu,
Iida Takashi,
Platt Frances,
Clayton Peter T.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12196
Subject(s) - glycine , bile acid , moiety , chemistry , biomarker , biochemistry , glycocholic acid , amino acid , stereochemistry , cholic acid
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, NPCBA 1 (3β‐hydroxy,7β‐ N ‐acetylglucosaminyl‐5‐cholenoic acid) and NPCBA 2 (probably 3β,5α,6β‐trihydroxycholanoyl‐glycine), were observed to accumulate preferentially in NPC patients: median plasma concentrations of NPCBA 1 and NPCBA 2 were 40‐ and 10‐fold higher in patients than in controls. However, NPCBA 1 concentrations were normal in some patients because they carried a common mutation inactivating the Glc NA c transferase required for the synthesis of this bile acid. NPCBA 2, not containing a Glc NA c moiety, is thus a better NPC biomarker.