title: Mutations of the GLA gene in young patients with stroke: the PORTYSTROKE study--screening genetic conditions in Portuguese young stroke patients.
abstract: OBJECTIVE
  Fabry disease is an X-linked monogenic disorder caused by mutations in the GLA gene. Recent data suggest that stroke in young adults may be associated with Fabry disease. We aimed to ascertain the prevalence of this disorder among young adult patients with stroke in Portugal by GLA genotyping.
  
  
  METHODS
  During 1 year, all patients aged 18 to 55 years with first-ever stroke, who were admitted into any of 12 neurology hospital departments in Portugal, were prospectively enrolled (n=625). Ischemic stroke was classified according to Trial of Org 10172 in Acute Stroke Treatment criteria. Alpha-galactosidase activity was further assayed in all patients with GLA mutations.
  
  
  RESULTS
  Four hundred ninety-three patients (mean age, 45.4 years; 61% male) underwent genetic analyses: 364 with ischemic stroke, 89 with intracerebral hemorrhage, 26 with subarachnoid hemorrhage, and 14 with cerebral venous thrombosis. Twelve patients had missense GLA mutations: 9 with ischemic stroke (p.R118C: n=4; p.D313Y: n=5), including 5 patients with an identified cause of stroke (cardiac embolism: n=2; small vessel disease: n=2; other cause: n=1), 2 with intracerebral hemorrhage (p.R118C: n=1; p.D313Y: n=1), and one with cerebral venous thrombosis (p.R118C: n=1). Leukocyte alpha-galactosidase activity was subnormal in the hemizygous males and subnormal or low-normal in the heterozygous females. Estimated prevalence of missense GLA mutations was 2.4% (95% CI, 1.3% to 4.1%).
  
  
  CONCLUSIONS
  Despite a low diagnostic yield, screening for GLA mutations should probably be considered in different types of stroke. Restricting investigation to patients with cryptogenic stroke may underestimate the true prevalence of Fabry disease in young patients with stroke.
authors.affiliation: Serviço de Neurologia, Hospital Garcia de Orta, 2801-951 Almada, Portugal. vbaptista@hgo.min-saude.pt
authors.forename: Miguel Viana
authors.initials: MV
authors.lastname: Baptista
authors.forename: Susana
authors.initials: S
authors.lastname: Ferreira
authors.forename: Teresa
authors.initials: T
authors.lastname: Pinho-E-Melo
authors.forename: Marta
authors.initials: M
authors.lastname: Carvalho
authors.forename: Vítor T
authors.initials: VT
authors.lastname: Cruz
authors.forename: Cátia
authors.initials: C
authors.lastname: Carmona
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Silva
authors.forename: Assunção
authors.initials: A
authors.lastname: Tuna
authors.forename: Miguel
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Carla
authors.initials: C
authors.lastname: Ferreira
authors.forename: Ana A N
authors.initials: AA
authors.lastname: Pinto
authors.forename: André
authors.initials: A
authors.lastname: Leitão
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Gabriel
authors.forename: Sofia
authors.initials: S
authors.lastname: Calado
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Oliveira
authors.forename: José M
authors.initials: JM
authors.lastname: Ferro
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D015331:Cohort Studies; D000795:Fabry Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D015995:Prevalence; D011446:Prospective Studies; D020521:Stroke / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase