Monserrat Lorenzo, Gimeno-Blanes Juan Ramón, Marín Francisco, Hermida-Prieto Manuel, García-Honrubia Antonio, Pérez Inmaculada, Fernández Xusto, de Nicolas Rosario, de la Morena Gonzalo, Payá Eduardo, Yagüe Jordi, Egido Jesús
Complejo Hospitalario Universitario Juan Canalejo, A Coruña, Spain.
J Am Coll Cardiol. 2007 Dec 18;50(25):2399-403. doi: 10.1016/j.jacc.2007.06.062.
We aimed to study the prevalence of Fabry disease (FD) in patients with hypertrophic cardiomyopathy (HCM).
There are limited and controversial data about the prevalence of FD in patients with HCM.
We screened the plasma alpha-galactosidase A activity from 508 unrelated patients with HCM (328 men, 180 women, ages 58 +/- 16 years). Patients with low activity (0% to 30% of the normal control in men, and 0% to 50% in women) underwent genetic study of the GLA gene.
We found low plasma activity in 15 patients (3%). Three men had GLA mutations (0.9%): S238N (novel) in 2 and E358del (described) in 1. Two women had described mutations (1.1%): L89P and A143T. Three unrelated men had the D313Y variant previously associated with enzyme pseudo-deficiency. Two women had polymorphisms that did not segregate with the disease in their families. Five women (activity 39% to 47%) had no sequence variants. The familial studies allowed the diagnosis of 14 carriers: 6 women without Fabry manifestations, 3 women with cardiomyopathy, 2 men with renal and cardiac disease, 1 man with microhematuria, 1 woman with first-degree atrioventricular block, and a 32-year-old woman with only renal disease.
By means of a screening based on genotyping of patients with low plasma enzymatic activity, the prevalence of FD in our population of HCM is 1% (0.9% in men and 1.1% in women). This diagnosis is relevant, because it allows the identification of disease carriers that might benefit from enzyme replacement therapy.
我们旨在研究肥厚型心肌病（HCM）患者中法布里病（FD）的患病率。
关于HCM患者中FD患病率的数据有限且存在争议。
我们对508例无亲缘关系的HCM患者（328例男性，180例女性，年龄58±16岁）的血浆α-半乳糖苷酶A活性进行了筛查。活性低的患者（男性为正常对照的0%至30%，女性为0%至50%）接受了GLA基因的遗传学研究。
我们发现15例患者（3%）血浆活性低。3名男性有GLA突变（0.9%）：2例为S238N（新发现），1例为E358del（已报道）。2名女性有已报道的突变（1.1%）：L89P和A143T。3名无亲缘关系的男性有先前与酶假性缺乏相关的D313Y变异。2名女性有在其家族中与疾病不连锁的多态性。5名女性（活性为39%至47%）无序列变异。家族研究确诊了14名携带者：6名无法布里病表现的女性，3名患有心肌病的女性，2名患有肾脏和心脏疾病的男性，1名有镜下血尿的男性，1名患有一度房室传导阻滞的女性，以及1名仅患有肾脏疾病的32岁女性。
通过对血浆酶活性低的患者进行基因分型筛查，我们的HCM患者群体中FD的患病率为1%（男性为0.9%，女性为1.1%）。这一诊断具有重要意义，因为它能够识别可能从酶替代疗法中获益的疾病携带者。
