Mutations of the GLA gene in young patients with stroke: the PORTYSTROKE study--screening genetic conditions in Portuguese young stroke patients.
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.
Baptista
Miguel Viana
MV
Serviço de Neurologia, Hospital Garcia de Orta, 2801-951 Almada, Portugal. vbaptista@hgo.min-saude.pt
Ferreira
Susana
S
Pinho-E-Melo
Teresa
T
Carvalho
Marta
M
Cruz
Vítor T
VT
Carmona
Cátia
C
Silva
Fernando A
FA
Tuna
Assunção
A
Rodrigues
Miguel
M
Ferreira
Carla
C
Pinto
Ana A N
AA
Leitão
André
A
Gabriel
João Paulo
JP
Calado
Sofia
S
Oliveira
João Paulo
JP
Ferro
José M
JM
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*
D000519:alpha-Galactosidase