title: Skin Globotriaosylceramide 3 Load Is Increased in Men with Advanced Fabry Disease.
abstract: BACKGROUND
  The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity.
  
  
  METHODS
  At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data.
  
  
  RESULTS
  We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy.
  
  
  CONCLUSIONS
  Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients.
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.|Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.|Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Schröter
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.|Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kafke
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.|Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kramer
authors.affiliation: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany.|Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany.|Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.|Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), University of Würzburg, Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003710:Demography; D000795:Fabry Disease / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012720:Severity of Illness Index; D012867:Skin / Q000294:innervation / Q000378:metabolism* / Q000473:pathology*; D014281:Trihexosylceramides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014281:Trihexosylceramides; C018549:globotriaosylceramide