Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme α-galactosidase A due to mutations in the GLA gene. This leads to an accumulation of globotriaosylceramide (GL-3) in many tissues, which results in progressive damage to the kidneys, heart, and nervous system. We present the molecular and clinical characteristics and long-term outcomes of FD patients from a multidisciplinary clinic at the University of California, Irvine treated with agalsidase beta enzyme replacement therapy (ERT) for 2–20 years. This cohort comprised 24 adults (11 males, 13 females) and two male children (median age 45; range 10–68 years). Of the 26 patients in this cohort, 20 were on ERT (12 males, 8 females). We describe one novel variant not previously reported in the literature in a patient with features of ‘classic’ FD. The vast majority of patients in this cohort presented with symptoms of ‘classic’ FD including peripheral neuropathic pain, some form of cardiac involvement, angiokeratomas, corneal verticillata, hypohidrosis, tinnitus, and gastrointestinal symptoms, primarily abdominal pain. The majority of males had clinically evident renal involvement. An annual eGFR reduction of −1.88 mL/min/1.73 m²/yr during the course of ERT was seen in this cohort. The most common renal presentation was proteinuria, and one individual required a renal transplant. Other common findings were pulmonary involvement, lymphedema, hearing loss, and significantly, three patients had strokes. Notably, there was a high prevalence of endocrine dysfunction and low bone mineral density, including several with osteoporosis.

While enzyme replacement therapy (ERT) cleared plasma GL-3 in this cohort, there was limited improvement in renal function or health-related quality of life based on the patient-reported SF-36 Health Survey. Physical functioning significantly declined over the course of ERT treatment, which may be, in part, due to the late initiation of ERT in several patients. Further delineation of the phenotypic and genotypic spectrum in patients with FD and the long-term outcome of ERT will help improve management and treatment options for this disease.

法布里病 (FD) 是一种 X 连锁溶酶体贮积症，由GLA基因突变导致 α-半乳糖苷酶 A 缺乏所致。这会导致三酰神经酰胺 (GL-3) 在许多组织中积聚，从而对肾脏、心脏和神经系统造成渐进性损害。我们介绍了来自加州大学欧文分校多学科诊所的 FD 患者接受阿加糖酶 β 酶替代疗法 (ERT) 2-20 年治疗的分子和临床特征以及长期结果。该队列由 24 名成年人（11 名男性，13 名女性）和两名男性儿童（中位年龄 45 岁；范围 10-68 岁）组成。在该队列的 26 名患者中，有 20 名接受 ERT（12 名男性，8 名女性）。我们描述了一种先前未在文献中报道过的、具有“经典”FD 特征的患者的新变异。该队列中的绝大多数患者出现“典型”FD 症状，包括周围神经性疼痛、某种形式的心脏受累、血管角化瘤、角膜轮状化、少汗、耳鸣和胃肠道症状（主要是腹痛）。大多数男性有临床明显的肾脏受累。在 ERT 过程中，该队列的 eGFR 每年降低 -1.88 mL/min/1.73 m ² /yr。最常见的肾脏症状是蛋白尿，其中一个人需要进行肾移植。其他常见的发现包括肺部受累、淋巴水肿、听力损失，值得注意的是，三名患者患有中风。值得注意的是，内分泌功能障碍和骨矿物质密度低的患病率很高，其中一些人患有骨质疏松症。

虽然酶替代疗法 (ERT) 清除了该队列中的血浆 GL-3，但根据患者报告的 SF-36 健康调查，肾功能或健康相关生活质量的改善有限。在 ERT 治疗过程中，身体机能显着下降，部分原因可能是由于一些患者较晚开始 ERT。进一步描述 FD 患者的表型和基因型谱以及 ERT 的长期结果将有助于改善该疾病的管理和治疗选择。