title: Urinary total globotriaosylceramide and isoforms to identify women with Fabry disease: a diagnostic test study.
abstract: BACKGROUND
  Fabry disease is a treatable X-linked lysosomal storage disorder caused by alterations in the structural gene (GLA) of α-galactosidase A (AGAL), manifesting with cardiovascular and/or kidney disease and decreased life span. Although males as well as females can be affected, females cannot be identified using AGAL activity. We evaluated urinary total globotriaosylceramide (Gb3) and single N-acyl isoforms for the detection of Fabry disease in female patients with and without chronic kidney disease (CKD).
  
  
  METHODS
  Diagnostic accuracy study.
  
  
  METHODS
  28 untreated women with Fabry disease and 335 female outpatients without Fabry disease with (n = 213) and without CKD (n = 122).
  
  
  METHODS
  Assessment of urinary Gb3 using electrospray ionization tandem mass spectrometry, including 6 N-acyl isoforms, total Gb3 related to urinary creatinine, and ratios of Gb3-24 to Gb3-18 and Gb3-24 to urinary AGAL.
  
  
  METHODS
  Fabry disease, diagnosed by identification of known pathogenic GLA mutations in patients or their male relatives.
  
  
  RESULTS
  6 parameters (ratio of Gb3-24 to urinary AGAL activity; Gb3-24; ratio of Gb3-24 to Gb3-18; Gb3-22; Gb3-16; and total Gb3) were highly informative for the diagnosis of Fabry disease independent of the presence or absence of CKD (area under the receiver operating characteristic curve, 0.876-0.927; all P < 0.001).
  
  
  CONCLUSIONS
  Because of low signal-to-noise ratios, 15.8% of samples had to be excluded.
  
  
  CONCLUSIONS
  Total urinary Gb3 and Gb3 isoforms can be used for the diagnosis of Fabry disease in women.
authors.affiliation: Department of Pediatrics, Medical University of Graz, Graz, Austria. eduard.paschke@medunigraz.at
authors.forename: Eduard
authors.initials: E
authors.lastname: Paschke
authors.forename: Guenter
authors.initials: G
authors.lastname: Fauler
authors.forename: Heimo
authors.initials: H
authors.lastname: Winkler
authors.forename: Axel
authors.initials: A
authors.lastname: Schlagenhauf
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Erwa
authors.forename: Frank
authors.initials: F
authors.lastname: Breunig
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Urban
authors.forename: Bojan
authors.initials: B
authors.lastname: Vujkovac
authors.forename: Gere
authors.initials: G
authors.lastname: Sunder-Plassmann
authors.forename: Peter
authors.initials: P
authors.lastname: Kotanko
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D003955:Diagnostic Tests, Routine / Q000379:methods; D000795:Fabry Disease / Q000175:diagnosis* / Q000652:urine*; D005260:Female; D006801:Humans; D008875:Middle Aged; D020033:Protein Isoforms / Q000652:urine; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014281:Trihexosylceramides / Q000652:urine*; D000519:alpha-Galactosidase / Q000652:urine
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase