De Brabander Isabel, Yperzeele Laetitia, Ceuterick-De Groote Chantal, Brouns Raf, Baker Robert, Belachew Shibeshih, Delbecq Jean, De Keulenaer Gilles, Dethy Sophie, Eyskens François, Fumal Arnaud, Hemelsoet Dimitri, Hughes Derralynn, Jeangette Sandrine, Nuytten Dirk, Redondo Patricia, Sadzot Bernard, Sindic Christian, Sheorajpanday Rishi, Thijs Vincent, Van Broeckhoven Christine, De Deyn Peter P
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Clin Neurol Neurosurg. 2013 Jul;115(7):1088-93. doi: 10.1016/j.clineuro.2012.11.003. Epub 2012 Dec 4.
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 α-galactosidase A (α-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 α-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.
在比利时法布里病研究（BeFaS）中，对1000名出现中风、不明原因白质病变或椎基底动脉延长扩张的年轻患者进行了法布里病患病率评估。BeFaS的结果表明，法布里病可能在高达1%的患有脑血管疾病的年轻患者中起作用。然而，在所有病例中临床相关性尚不清楚。我们报告了在BeFaS中鉴定出的α - 半乳糖苷酶A（α - Gal A）酶缺乏或GLA突变的受试者（n = 10）的详细表型分析，以及该人群的家族筛查结果。
进行家族筛查以识别其他突变携带者。对所有受试者（BeFaS索引患者和携带GLA突变的亲属）进行生化和/或临床评估。
基因家族筛查发现另外18名GLA突变携带者。所有GLA突变携带者的血斑α - Gal A酶活性均正常，即使是2名携带p.A143T突变的男性也是如此。所有受试者的血浆Gb3和溶酶体Gb3水平均正常。2名受试者尿液中检测到Gb3升高。在我们的人群中未检测到一些法布里病的典型临床体征，如血管角质瘤或涡状角膜。10名p.A143T携带者中有6人出现法布里病的心脏症状。携带GLA突变的亲属中未发现脑血管疾病迹象。
在我们的脑血管疾病人群中，我们未能识别出导致法布里病经典临床表型的突变。血斑和血浆中的酶活性分析可能无法识别法布里病的迟发型变体。当怀疑男性脑血管疾病患者患有非典型、迟发型法布里病变体时，我们建议进行基因检测。然而，这可能会识别出非致病或有争议的基因变体。
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