Fabry's disease (FD) is an X‐linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α‐galactosidase A (α‐Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous α‐Gal A activity. We assessed safety along with cardiovascular, renal, and patient‐reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under “real‐world” conditions. Fifty‐nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) with amenable mutations were recruited. Migalastat was generally safe and well tolerated. Females and males presented with a reduction of left ventricular mass index (primary end point) (−7.2 and −13.7 g/m², P  = 0.0050 and P  = 0.0061). FD‐specific manifestations and symptoms remained stable (all P > 0.05). Both sexes presented with a reduction of estimated glomerular filtration rate (secondary end point) (−6.9 and −5.0 mL/minute/1.73 m²; P  = 0.0020 and P  = 0.0004, respectively), which was most prominent in patients with low blood pressure (P  = 0.0271). α‐Gal A activity increased in male patients by 15% from 29% to 44% of the normal wild‐type activity (P  = 0.0106) and plasma lyso‐Gb3 levels were stable in females and males (P  = 0.3490 and P  = 0.2009). Reevaluation of mutations with poor biochemical response revealed no marked activity increase in a zero activity background. We conclude that therapy with migalastat was generally safe and resulted in an amelioration of left ventricular mass. In terms of impaired renal function, blood pressure control seems to be an unattended important goal.

中文翻译：

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用米格司他治疗法布里氏病：一项前瞻性观察性多中心研究的结果（著名）。

法布里氏病（FD）是一种X连锁的溶酶体贮积病，由溶酶体酶α-半乳糖苷酶A（α-GalA）的活性不足引起，导致globotriaosylceramide（Gb3）在细胞内积聚。可以接受突变的患者可以使用migalastat治疗，这是一种最近被批准的口服药理伴侣，可以增加内源性α-GalA的活性。在“现实世界”条件下进行migalastat治疗12个月后，我们通过一项前瞻性观察性多中心研究评估了安全性以及心血管，肾脏和患者报告的结局以及疾病生物标志物。招募了五十九名（28名女性）具有适当突变的患者（34名（57.6％）接受了酶替代治疗）。Migalastat一般安全且耐受良好。²，P  ＝ 0.0050，P  ＝ 0.0061。FD特定的表现和症状保持稳定（所有P > 0.05）。男性和女性的肾小球滤过率估计值均降低（次级终点）（分别为-6.9和-5.0 mL /分钟/1.73 m ²；P  = 0.0020和P  = 0.0004），这在低血脂患者中最为明显压力（P  = 0.0271）。男性患者的α‐Gal A活性从正常野生型活动的29％增至44％（P  = 0.0106），增加了15％，并且血浆溶血Gb3水平在女性和男性中均保持稳定（P  = 0.3490和P = 0.2009）。对生化反应较差的突变的重新评估显示，零活性背景下的活性没有明显增加。我们得出的结论是，使用米加司他治疗通常是安全的，并且可以改善左心室质量。就肾功能受损而言，控制血压似乎是一个无人值守的重要目标。