title: Screening for Fabry Disease by Urinary Globotriaosylceramide Isoforms Measurement in Patients with Left Ventricular Hypertrophy.
abstract: BACKGROUND
  Left ventricular hypertrophy (LVH) is a frequent echocardiographic feature in Fabry disease (FD) and in severe cases may be confused with hypertrophic cardiomyopathy (HCM) of other origin. The prevalence of FD in patients primarily diagnosed with HCM varies considerably in screening and case finding studies, respectively. In a significant proportion of patients, presenting with only mild or moderate LVH and unspecific clinical signs FD may remain undiagnosed. Urinary Gb3 isoforms have been shown to detect FD in both, women and men. We examined whether this non-invasive method would help to identify new FD cases in a non-selected cohort of patients with various degree of LVH.
  
  
  RESULTS
  Consecutive patients older than 18 years with a diastolic interventricular septal wall thickness of ≥12mm determined by echocardiography were included. Referral diagnosis was documented and spot urine was collected. Gb3 was measured by mass spectroscopy. Subjects with an elevated Gb3-24:18 ratio were clinically examined for signs of FD, α-galactosidase-A activity in leukocytes was determined and GLA-mutation-analysis was performed. We examined 2596 patients. In 99 subjects urinary Gb3 isoforms excretion were elevated. In these patients no new cases of FD were identified by extended FD assessment. In two of three patients formerly diagnosed with FD Gb3-24:18 ratio was elevated and would have led to further diagnostic evaluation.
  
  
  CONCLUSIONS
  Measurement of urinary Gb3 isoforms in a non-selected cohort with LVH was unable to identify new cases of FD. False positive results may be prevented by more restricted inclusion criteria and may improve diagnostic accuracy of this method.
authors.affiliation: 1. Department of Medicine II, Division of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.; 2. Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Gaggl
authors.affiliation: 1. Department of Medicine II, Division of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Natalija
authors.initials: N
authors.lastname: Lajic
authors.affiliation: 3. Center of Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.affiliation: 4. Department of Clinical Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Till
authors.initials: T
authors.lastname: Voigtländer
authors.affiliation: 5. Department of Laboratory Medicine, Laboratory for Molecular Diagnostics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Raute
authors.initials: R
authors.lastname: Sunder-Plassmann
authors.affiliation: 6. Department of Pediatrics, Medical University of Graz, Auenbruggerplatz, 8036 Graz, Austria.
authors.forename: Eduard
authors.initials: E
authors.lastname: Paschke
authors.affiliation: 7. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz, 8036 Graz, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Fauler
authors.affiliation: 2. Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Gere
authors.initials: G
authors.lastname: Sunder-Plassmann
authors.affiliation: 1. Department of Medicine II, Division of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Mundigler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004452:Echocardiography; D000795:Fabry Disease / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine; D005260:Female; D006017:Glycolipids / Q000652:urine; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization; D014281:Trihexosylceramides / Q000652:urine*; D000519:alpha-Galactosidase / Q000378:metabolism
chemical_list: D006017:Glycolipids; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase
keywords: Fabry disease; case-finding study; left ventricular hypertrophy; urinary Gb3 isoforms