Arends Maarten, Wanner Christoph, Hughes Derralynn, Mehta Atul, Oder Daniel, Watkinson Oliver T, Elliott Perry M, Linthorst Gabor E, Wijburg Frits A, Biegstraaten Marieke, Hollak Carla E
Departments of Endocrinology and Metabolism and
Department of Internal Medicine I, Division of Cardiology and Nephrology, Comprehensive Heart Failure Center and Fabry Center for Interdisciplinary Therapy, University Hospital Wuerzburg, Wuerzburg, Germany.
J Am Soc Nephrol. 2017 May;28(5):1631-1641. doi: 10.1681/ASN.2016090964. Epub 2016 Dec 15.
Fabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00; <0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40; <0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype (<0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients.
法布里病会导致肾脏、心脏和脑血管方面的表现。典型和非典型受累患者之间的表型差异很明显，但关于男性和女性典型及非典型疾病自然病程的数据却很少。为了描述按性别和表型分层的法布里病自然病程，我们对来自三个国际卓越中心的499例成年患者（平均年龄43岁；41%为男性；57%具有典型表型）从出生到首次临床就诊（在酶替代治疗之前）的无事件生存期进行了回顾性评估。我们根据特征性症状和酶活性对患者进行表型分类。典型法布里病的男性和女性比非典型疾病患者的事件发生率更高（男性风险比为5.63，95%置信区间为3.17至10.00；<0.001；女性风险比为2.88，95%置信区间为1.54至5.40；<0.001）。此外，典型法布里病男性的估算肾小球滤过率（eGFR）较低、左心室质量较高、血浆球三糖基鞘氨醇浓度较高，高于非典型法布里病男性或任何一种表型的女性（<0.001）。总之，在进行酶替代治疗之前，典型法布里病男性比非典型疾病男性或任何一种表型的女性有更多的事件发生史；典型法布里病女性比非典型疾病女性更易发生并发症。这些数据可能支持制定法布里病监测和治疗的新指南以及对患者亚组干预效果的研究。
