title: Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease.
abstract: OBJECTIVE
  Data on the prevalence of Fabry disease in patients with central nervous system pathology are limited and controversial. In this study, we assessed the prevalence of Fabry disease in young patients presenting with cerebrovascular disease in Belgium.
  
  
  METHODS
  In this national, prospective, multicenter study, we screened for Fabry disease in 1000 patients presenting with ischemic stroke, transient ischemic attack, or intracranial hemorrhage; unexplained white matter lesions; or vertebrobasilar dolichoectasia. In male patients, we measured alpha-galactosidase A (alpha-GAL A) activity in dried blood spots. Female patients were screened for mutations by exonic DNA sequencing of the alpha-GAL A gene.
  
  
  RESULTS
  alpha-GAL A activity was deficient in 19 men (3.5%), although all had normal alpha-GAL A gene sequences. Enzymatic deficiency was confirmed on repeat assessment in 2 male patients (0.4%). We identified missense mutations in 8 unrelated female patients (1.8%): Asp313Tyr (n=5), Ala143Thr (n=2), and Ser126Gly (n=1). The pathogenicity of the 2 former missense mutations is controversial. Ser126Gly is a novel mutation that can be linked to late-onset Fabry disease.
  
  
  CONCLUSIONS
  alpha-GAL A deficiency may play a role in up to 1% of young patients presenting with cerebrovascular disease. These findings suggest that atypical variants of Fabry disease with late-onset cerebrovascular disease exist, although the clinical relevance is unclear in all cases.
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, and Department of Biomedical Sciences, University of Antwerp-CDE, Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Raf
authors.initials: R
authors.lastname: Brouns
authors.forename: Vincent
authors.initials: V
authors.lastname: Thijs
authors.forename: François
authors.initials: F
authors.lastname: Eyskens
authors.forename: Marleen
authors.initials: M
authors.lastname: Van den Broeck
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Patricia
authors.initials: P
authors.lastname: Redondo
authors.forename: Dimitri
authors.initials: D
authors.lastname: Hemelsoet
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fumal
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jeangette
authors.forename: Werner
authors.initials: W
authors.lastname: Verslegers
authors.forename: Robert
authors.initials: R
authors.lastname: Baker
authors.forename: Derralynn
authors.initials: D
authors.lastname: Hughes
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001530:Belgium / Q000453:epidemiology; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D000795:Fabry Disease / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics
chemical_list: D000519:alpha-Galactosidase