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 -galactosidase A (-GAL A) activity in dried blood spots.
Female patients were screened for mutations by exonic DNA sequencing of the -GAL A gene. Results---GAL A activity was deficient in 19 men (3.5%), although all had normal -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 (n5), Ala143Thr (n2), and Ser126Gly (n1). 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---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.
dolichoectasia. In male patients, we measured -galactosidase A (-GAL A) activity in dried blood spots.
Female patients were screened for mutations by exonic DNA sequencing of the -GAL A gene. Results---GAL A activity was deficient in 19 men (3.5%), although all had normal -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 (n5), Ala143Thr (n2), and Ser126Gly (n1). 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---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.
| Original language | English |
|---|---|
| Pages (from-to) | 863-868 |
| Number of pages | 6 |
| Journal | Stroke |
| Volume | 41 |
| Issue number | 5 |
| Publication status | Published - May 2010 |
Keywords
- Fabry disease
- cerebrovascular accident
- white matter lesions
- dolichoectasia
- -galactosidase A
- lysosomal storage disorders
- Belgium