title: Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.
abstract: A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, 03722, Republic of Korea.
authors.forename: Seul Kee
authors.initials: SK
authors.lastname: Byeon
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, 03722, Republic of Korea.
authors.forename: Jin Yong
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. jinsunglee@yuhs.ac.
authors.forename: Jin-Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, 03722, Republic of Korea. mhmoon@yonsei.ac.kr.
authors.forename: Myeong Hee
authors.initials: MH
authors.lastname: Moon
mesh_terms: D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods*; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000188:drug therapy*; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000652:urine*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D008055:Lipids; D000519:alpha-Galactosidase
keywords: Enzyme replacement therapy; Fabry disease; Lipid; Nanoflow UPLC-ESI-MS/MS; Trihexosylceramide (THC)