Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease.
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.
Brouns
Raf
R
Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, and Department of Biomedical Sciences, University of Antwerp-CDE, Universiteitsplein 1, 2610 Antwerp, Belgium.
Thijs
Vincent
V
Eyskens
François
F
Van den Broeck
Marleen
M
Belachew
Shibeshih
S
Van Broeckhoven
Christine
C
Redondo
Patricia
P
Hemelsoet
Dimitri
D
Fumal
Arnaud
A
Jeangette
Sandrine
S
Verslegers
Werner
W
Baker
Robert
R
Hughes
Derralynn
D
De Deyn
Peter Paul
PP
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
D000519:alpha-Galactosidase