title: Biomarkers associated with clinical manifestations in Fabry disease patients with a late-onset cardiac variant mutation.
abstract: BACKGROUND
  Fabry disease is a lysosomal storage disorder with an incidence of 1:1600 for the late-onset IVS4+919G>A cardiac variant mutation in Taiwan. Signs and symptoms of this cardiac variant include left ventricular hypertrophy, mitral insufficiency and/or arrhythmias. The search for biomarkers that might predict the clinical outcomes and guide treatment options is important. We thus investigated relationships between Fabry disease biomarkers (such as globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues) and age, gender, enzyme activity, clinical manifestations and severity of the disease in these patients.
  
  
  METHODS
  Urine and plasma biomarkers were analyzed using tandem mass spectrometry. A large cohort of 191 adult and pediatric Fabry patients carrying the IVS4+919G>A mutation was studied. Some patients were members of the same family.
  
  
  RESULTS
  Our results show that the plasma lyso-Gb3level, and urinary analogue levels of lyso-Gb3at m/z (+16), (+34), and (+50) adjusted for gender and age had a positive association with the left ventricular mass index, and/or the Mainz Severity Score Index.
  
  
  CONCLUSIONS
  It might thus be of particular interest to monitor children with high levels of these biomarkers, as part of a longitudinal study in order to determine if the excretion profile at a young age is predictive of the outcomes of disease severity in adulthood.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada. Electronic address: christiane.auray-blais@usherbrooke.ca.
authors.forename: Christiane
authors.initials: C
authors.lastname: Auray-Blais
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lavoie
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Boutin
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada.
authors.forename: Aimé
authors.initials: A
authors.lastname: Ntwari
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Ting-Rong
authors.initials: TR
authors.lastname: Hsu
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Chun-Kai
authors.initials: CK
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002648:Child; D000795:Fabry Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006017:Glycolipids / Q000032:analysis / Q000097:blood; D006331:Heart Diseases / Q000235:genetics; D006801:Humans; D000067562:Late Onset Disorders / Q000235:genetics; D008297:Male; D009154:Mutation; D012720:Severity of Illness Index; D012737:Sex Factors; D013107:Sphingolipids / Q000032:analysis / Q000097:blood; D013624:Taiwan
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid
keywords: Biomarkers; Cardiac variant mutation; Fabry disease; Gb(3); IVS4+919G>A mutation; Lyso-Gb(3) and analogues; Mass spectrometry