Auray-Blais C.Ntwari A.Clarke J.T.R.Warnock D.G.Oliveira J.P.Young S.P.Millington D.S.Bichet D.G.Sirrs S.West M.L.Casey R.WUH-LIANG HWUKeutzer J.M.Zhang X.K.Gagnon R.2020-12-162020-12-1620100009-8981https://www.scopus.com/inward/record.uri?eid=2-s2.0-77957756430&doi=10.1016%2fj.cca.2010.07.038&partnerID=40&md5=7aabee292854d3e2d6c3f5cfa0e764fbhttps://scholars.lib.ntu.edu.tw/handle/123456789/525925Background: Fabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb3), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb3), is increased in patients with the disease. Until now, lyso-Gb3 was not detectable in urine, possibly because of the presence of interfering compounds. Methods: We undertook to: 1) characterize lyso-Gb3 in urine; 2) develop a method to quantitate urinary lyso-Gb3 by mass spectrometry; 3) evaluate urinary lyso-Gb3 as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb3 is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb3 from 83 Fabry patients and 77 healthy age-matched controls. Results: The intraday and interday bias and precision of the method were <15%. Increases in lyso-Gb3/creatinine correlated with the concentrations of Gb3 (r2=0.43), type of mutations (p=0.0006), gender (p<0.0001) and enzyme replacement therapy status (p=0.0012). Urine from healthy controls contained no detectable lyso-Gb3. Lyso-Gb3 did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb3 of Fabry patients correlated well with a number of indicators of disease severity. Conclusion: Lyso-Gb3 is a reliable independent biomarker for clinically important characteristics of Fabry disease. ? 2010 Elsevier B.V.Fabry disease; LC-MS/MS; Liquid chromatography-tandem mass spectrometry; Time-of-flight mass spectrometry[SDGs]SDG3agalsidase alfa; agalsidase beta; alpha galactosidase; biological marker; creatinine; globotriaosylceramide; globotriaosylsphingosine; unclassified drug; alpha galactosidase; biological marker; creatine; drug derivative; globotriaosyl lysosphingolipid; glycolipid; psychosine; sphingolipid; sphingosyl beta glucoside; sphingosyl beta-glucoside; adult; aged; article; controlled study; creatinine blood level; disease severity; enzyme activity; enzyme inhibition; enzyme replacement; Fabry disease; female; gene mutation; human; kidney function; liquid chromatography; major clinical study; male; priority journal; tandem mass spectrometry; time of flight mass spectrometry; urinary excretion; urine level; validation process; adolescent; case control study; child; drug antagonism; enzymology; Fabry disease; kidney; methodology; middle aged; pathophysiology; preschool child; reproducibility; sex difference; standard; urinalysis; urine; Adolescent; Adult; Aged; alpha-Galactosidase; Biological Markers; Case-Control Studies; Child; Child, Preschool; Creatine; Fabry Disease; Female; Glycolipids; Humans; Kidney; Male; Middle Aged; Psychosine; Reference Standards; Reproducibility of Results; Sex Factors; Sphingolipids; Urinalysis; Young Adultjournal article10.1016/j.cca.2010.07.038207164422-s2.0-77957756430