Fabry disease is a rare genetic disease that is part of a group of conditions called lysosomal storage diseases. It is characterized by an abnormal accumulation of glycosphingolipids, a subclass of glycolipids which are important components of the body’s cell membranes. This accumulation is caused by a reduction in, or absence of, enzyme α-Gal A activity, which normally breaks glycosphingolipids down into smaller units, avoiding their accumulation. The absence or reduction in the α-Gal A enzyme activity is caused by mutations (changes in the normal DNA sequence) in the GLA gene. Migalastat is an oral treatment for Fabry patients with GLA mutations that respond to this treatment. We report a case of a 60-year-old male patient with Fabry disease, presenting with two GLA mutations (p.R356Q and p.G360R). Although these mutations are individually amenable to migalastat, their combination and interaction in the same chromosome precludes response to this treatment. This case illustrates how therapeutic decisions for treating Fabry disease can be challenging depending on the mutations causing the disease and how genetic material is decisive for therapy selection.
法布里病是一种罕见的遗传病,是一组称为溶酶体贮积病的疾病的一部分。它的特征是鞘糖脂的异常积累,糖脂的一个亚类,是人体细胞膜的重要组成部分。这种积累是由减少引起的,或者没有,酶α-GalA活性,通常将鞘糖脂分解成更小的单位,避免积累。α-GalA酶活性的缺失或降低是由GLA基因的突变(正常DNA序列的变化)引起的。Migalastat是对GLA突变的Fabry患者的口服治疗,对这种治疗有反应。我们报告了一例60岁的男性患者患有法布里病,呈现两个GLA突变(p。R356Q和p.G360R)。尽管这些突变单独适用于migalastat,它们在同一染色体中的组合和相互作用排除了对这种治疗的反应。这个案例说明了治疗法布里病的治疗决策如何具有挑战性,这取决于导致疾病的突变以及遗传物质如何决定治疗选择。