Fabry is an X-linked disorder of glycosphingolipid metabolism that is caused by variants of the GLA gene that codes for α-galactosidase A, leading to lysosomal accumulation of globotriaosylceramide in many cell types. As a result, affected patients manifest with an increased risk of developing ischemic stroke, peripheral neuropathy, cardiac dysfunction, and chronic kidney disease. The protective effects of enzyme replacement therapy (ERT), the milestone in Fabry disease treatment, against globotriaosylceramide (GL-3) accumulation and Fabry disease progression are well known. However, the mechanism of action of ERT is not well understood. Since GL-3 also accumulates in the vascular endothelium, we investigated the effects of agalsidase-β, a recombinant human α-Gal enzyme approved for the treatment of Fabry disease. In this study, vascular function and blood pressure in four adult siblings affected by Fabry disease were evaluated upon agalsidase-β. In all patients, agalsidase-β infusion improves flow-mediated dilation and augmentation index. These changes occurred after the first infusion and were then maintained for the whole period of observation, i.e., 1 year, with more pronounced additional increments in flow-mediated dilation after the second agalsidase-β infusion. Blood pressure was also maintained at optimal levels in all of the patients for the whole period of observation. Our findings show that agalsidase-β administration can improve vascular function in patients suffering from Fabry disease. Changes in flow-mediated dilation and augmentation index persisted for the whole period of observation (1 year), thus suggesting that early substitutive therapy should be promoted in order to protect the cardiovascular system.

Fabry 是一种 X 连锁的鞘糖脂代谢疾病，由编码 α-半乳糖苷酶 A 的 GLA 基因变异引起，导致球三糖神经酰胺在许多细胞类型中的溶酶体积累。因此，受影响的患者出现缺血性中风、周围神经病变、心功能不全和慢性肾病的风险增加。酶替代疗法 (ERT) 是法布里病治疗的里程碑，其对球三糖神经酰胺 (GL-3) 积累和法布里病进展的保护作用是众所周知的。然而，ERT 的作用机制尚不清楚。由于 GL-3 也在血管内皮中积累，我们研究了 agalsidase-β 的作用，这是一种被批准用于治疗法布里病的重组人 α-Gal 酶。在这项研究中，在 agalsidase-β 上评估了四个受法布里病影响的成年兄弟姐妹的血管功能和血压。在所有患者中，阿加糖酶-β 输注改善了血流介导的扩张和增强指数。这些变化发生在第一次输注后，然后在整个观察期（即 1 年）中保持不变，在第二次阿加糖酶-β 输注后流量介导的扩张增加更明显。在整个观察期间，所有患者的血压也保持在最佳水平。我们的研究结果表明，阿加糖酶-β 给药可以改善法布里病患者的血管功能。流量介导的扩张和增强指数的变化在整个观察期间（1 年）持续存在，