Prevalence of Fabry Disease in Young Patients with Stroke in Argentina

J Stroke Cerebrovasc Dis. 2018 Mar;27(3):575-582. doi: 10.1016/j.jstrokecerebrovasdis.2017.09.045. Epub 2017 Nov 11.

Abstract

Background: Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina.

Methods: This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemic or hemorrhagic stroke within the previous 180 days. FD was diagnosed by measuring α-galactosidase A activity (males) and through genetic studies (females).

Results: We enrolled 311 patients (54% men, mean age: 41 years). Ischemic events occurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in 11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes) had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene. Her only other manifestation of FD was angiokeratoma. Eighteen females had nonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients had the nonpathogenic mutation D313Y, while a third had the likely benign mutation S126G.

Conclusions: FD was identified in 1 patient (.3%) in this first Latin American study. The patient presented with a late-onset oligo-symptomatic form of the disease. A large number of nonpathogenic mutations were present in our cohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment.

Keywords: Fabry disease; cerebrovascular disease; mutations; stroke; young.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Argentina / epidemiology
  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / epidemiology*
  • DNA Mutational Analysis
  • Fabry Disease / diagnosis
  • Fabry Disease / epidemiology*
  • Fabry Disease / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Ischemic Attack, Transient / diagnosis
  • Ischemic Attack, Transient / epidemiology*
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Prevalence
  • Prospective Studies
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / epidemiology*
  • Time Factors
  • Young Adult
  • alpha-Galactosidase / genetics

Substances

  • GLA protein, human
  • alpha-Galactosidase