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Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease

(2010) STROKE. 41(5). p.863-868
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Abstract
Background and Purpose: 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. Conclusion: 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.
Keywords
cerebrovascular accident, white matter lesions, Fabry disease, dolichoectasia, alpha-galactosidase A, lysosomal storage disorders, Belgium, HYPERTROPHIC CARDIOMYOPATHY, TRANSPLANT RECIPIENTS, CRYPTOGENIC STROKE, MANIFESTATIONS, MUTATIONS, THERAPY, VARIANT

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Chicago
Brouns, Raf, Vincent Thijs, François Eyskens, Marleen Van den Broeck, Shibeshih Belachew, Christine Van Broeckhoven, Patricia Redondo, et al. 2010. “Belgian Fabry Study: Prevalence of Fabry Disease in a Cohort of 1000 Young Patients with Cerebrovascular Disease.” Stroke 41 (5): 863–868.
APA
Brouns, R., Thijs, V., Eyskens, F., Van den Broeck, M., Belachew, S., Van Broeckhoven, C., Redondo, P., et al. (2010). Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease. STROKE, 41(5), 863–868.
Vancouver
1.
Brouns R, Thijs V, Eyskens F, Van den Broeck M, Belachew S, Van Broeckhoven C, et al. Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease. STROKE. 2010;41(5):863–8.
MLA
Brouns, Raf, Vincent Thijs, François Eyskens, et al. “Belgian Fabry Study: Prevalence of Fabry Disease in a Cohort of 1000 Young Patients with Cerebrovascular Disease.” STROKE 41.5 (2010): 863–868. Print.
@article{1227730,
  abstract     = {Background and Purpose: 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.
Conclusion: 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.},
  author       = {Brouns, Raf and Thijs, Vincent and Eyskens, Fran\c{c}ois and Van den Broeck, Marleen and Belachew, Shibeshih and Van Broeckhoven, Christine and Redondo, Patricia and Hemelsoet, Dimitri and Fumal, Arnaud and Jeangette, Sandrine and Verslegers, Werner and Baker, Robert and Hughes, Derralynn and De Deyn, Peter Paul},
  issn         = {0039-2499},
  journal      = {STROKE},
  keyword      = {cerebrovascular accident,white matter lesions,Fabry disease,dolichoectasia,alpha-galactosidase A,lysosomal storage disorders,Belgium,HYPERTROPHIC CARDIOMYOPATHY,TRANSPLANT RECIPIENTS,CRYPTOGENIC STROKE,MANIFESTATIONS,MUTATIONS,THERAPY,VARIANT},
  language     = {eng},
  number       = {5},
  pages        = {863--868},
  title        = {Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease},
  url          = {http://dx.doi.org/10.1161/STROKEAHA.110.579409},
  volume       = {41},
  year         = {2010},
}

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