Phenotypical characterization of alpha-galacatosidase A gene mutations in a large Fabry disease screening program in stroke in the young

Isabelle De Brabander, Laetitia Yperzeele, Chantal Ceuteric-De Groote, Raf Brouns, Robert Baker, S Belachew, Jean Delbecq, Gilles De Keulenaer, Sophie Dethy, Francois Eyskens, A Fumal, J Groener, J. Aerts, D Hemelsoet, D Hughes, S Jeangette, Dirk Nuytten, P Redondo, Bernard Sadzot, Cj. SindicV Thijs, C. Van Broeckhoven, Peter Paul De Deyn

Research output: Contribution to journalArticle

24 Citations (Scopus)



In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia. The results of the BeFaS suggested that Fabry disease may play a role in up to 1% of young patients presenting with cerebrovascular disease. However, the clinical relevance was unclear in all cases. We report on detailed phenotyping in subjects identified with ?-galactosidase A (?-Gal A) enzyme deficiency or GLA mutations identified in the BeFaS (n=10), and on the results of family screening in this population.


Family screening was performed to identify additional mutation carriers. Biochemical and/or clinical evaluation of all subjects (BeFaS index patients and relatives carrying a GLA mutation) was performed.


Genetic family screening revealed 18 additional GLA mutation carriers. Bloodspot ?-Gal A enzyme activity was normal in all GLA mutation carriers, even in 2 males with the p.A143T mutation. Plasma Gb3 and lyso-Gb3 levels were normal in all subjects. Elevated Gb3 in urine was detected in 2 subjects. Some classic clinical signs of Fabry disease, like angiokeratoma or cornea verticillata, could not be detected in our population. Cardiac symptoms of Fabry disease were found in 6 out of 10 p.A143T carriers. No signs of cerebrovascular disease were found in the relatives with a GLA mutation.


We could not identify mutations causing the classical clinical phenotype of Fabry disease in our cerebrovascular disease population. Enzyme activity analysis in bloodspots and plasma may fail to identify late-onset variants of Fabry disease. We recommend genetic testing when an atypical, late-onset variant of Fabry disease is suspected in a male cerebrovascular disease patient. However, this may lead to the identification of non-disease causing or controversial genetic variants.
Original languageEnglish
Pages (from-to)1088-1093
JournalClin Neurol Neurosurg
Issue number7
Early online date4 Dec 2012
Publication statusPublished - 2013


  • Stroke
  • Fabry disease
  • Genetic screening


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