title: Identification of Two Sulfated Cholesterol Metabolites Found in the Urine of a Patient with Niemann-Pick Disease Type C as Novel Candidate Diagnostic Markers.
abstract: In the urine of a Niemann-Pick disease type C (NPC) patient, we have identified three characteristic intense peaks that have not been observed in the urine of a 3β-hydroxysteroid-Δ5-C27-steroid dehydrogenase deficiency patient or a healthy infant and adult. Based on accurate masses of the protonated molecules, we focused on two of them as candidate NPC diagnostic markers. Two synthesized authentic preparations agreed with the two compounds found in NPC patient urine in regard to both chromatographic behavior and accurate masses of the deprotonated molecules. Moreover, the isotopic patterns of the deprotonated molecules, twin peaks unique to the sulfur-containing compounds appearing in their second isotope positions, and accurate masses of product ions observed atm/z97 also agreed between the target compounds and authentic preparations. We identified the two compounds as the sulfated cholesterol metabolites as 3β-sulfooxy-7β-hydroxy-5-cholen-24-oic acid and 3β-sulfooxy-7-oxo-5-cholen-24-oic acid. These two compounds represent more promising candidate diagnostic markers for NPC diagnosis than three other candidates that are multiple conjugates of cholesterol metabolites, 3β-sulfooxy-7β-N-acetylglucosaminyl-5-cholen-24-oic acid and its glycine and taurine conjugates, although we have reported an analytical method for determining the urinary levels of these compounds using liquid chromatography/electrospray ionization tandem mass spectrometry, because of their lack ofN-acetylglucosamine conjugation.
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Maekawa
authors.affiliation: College of Humanities and Sciences, Nihon University.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Omura
authors.affiliation: College of Humanities and Sciences, Nihon University.
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Sekiguchi
authors.affiliation: College of Humanities and Sciences, Nihon University.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital; Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saigusa
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital.
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
keywords: Niemann–Pick disease type C; diagnostic markers; high-resolution mass spectrometry; metabolite identification; sulfated cholesterol metabolites