Division of Neurology, Department of Medicine, Centre hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada.
J Stroke Cerebrovasc Dis. 2013 Nov;22(8):1288-92. doi: 10.1016/j.jstrokecerebrovasdis.2012.10.005. Epub 2012 Nov 17.
A German study diagnosed 4% of young cryptogenic ischemic stroke patients with Fabry disease, an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (α-GAL-A) gene resulting in an accumulation of glycosphingolipids. A lower prevalence was found in other geographic regions.
To determine the prevalence of Fabry disease in a Canadian population of young cryptogenic ischemic stroke patients.
Patients with cryptogenic ischemic stroke at age 16-55 were retrospectively identified in our institutional stroke database and underwent a focused clinical evaluation. We sequenced the α-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine.
Ninety-three of 100 study subjects had normal α-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval, <.01%-6%). No subjects had angiokeratomas or other clinical manifestations of Fabry disease. Investigation results suggestive of Fabry disease (idiopathic hypertrophic cardiomyopathy, proteinuria, vertebrobasilar dolichoectasia, and the pulvinar sign) were found only in subjects with normal α-GAL-A genes. Apart from the 100 study subjects, our database included another patient with a family history of Fabry disease and a pathogenic mutation identified before her ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke.
Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening.
一项德国研究诊断出 4%的年轻隐源性缺血性卒中患者患有法布雷病，这是一种 X 连锁溶酶体贮积病，由α-半乳糖苷酶 A（α-GAL-A）基因突变引起，导致糖鞘脂的积累。在其他地理区域发现的患病率较低。
确定法布雷病在加拿大年轻隐源性缺血性卒中患者人群中的患病率。
我们在机构的卒中数据库中回顾性地确定了年龄在 16-55 岁的隐源性缺血性卒中患者，并对其进行了重点临床评估。我们对α-GAL-A 基因进行了测序，并在致病性不确定的突变患者中测量了血液 globotriaosylsphingosine 的水平。在有致病性突变或血液 globotriaosylsphingosine 水平升高的患者中诊断为法布雷病。
93 名研究对象的α-GAL-A 基因均无正常多态性。7 名患者有致病性不确定的突变，其中 1 名患者血液 globotriaosylsphingosine 水平升高（患病率 1%；95%置信区间，<.01%-6%）。无患者有血管角质瘤或法布雷病的其他临床表现。除了 100 名研究对象外，我们的数据库还包括另一名有法布雷病家族史的患者，以及一名在缺血性卒中发病前发现的致病性突变患者，这是法布雷病的首次临床表现。两名法布雷病患者均经历了复发性缺血性卒中。
法布雷病占加拿大年轻隐源性缺血性卒中患者的一小部分。鉴定法布雷病的生物标志物仍然是研究的重点，以明确需要常规筛查的卒中患者。
