PDF(Pubmed)
Abstract：
Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder that commonly manifests cardiovascular complications. We aimed to assess the prevalence of FD in a Chinese population with left ventricular hypertrophy (LVH) whilst implementing a gender-specific screening approach. Methods: Patients with LVH, defined as a maximum thickness of the left ventricular septal/posterior wall ≥ 13 mm, were considered eligible. All patients with hypertrophic cardiomyopathy (HCM) were excluded. Plasma α-galactosidase (α-GLA) enzyme activity was assessed using a dried blood spot test. Males with low enzyme activity underwent genetic testing to confirm a diagnosis of FD whereas females were screened for both α-GLA and globotriaosylsphingosine concentration and underwent genetic analysis of the GLA gene only if testing positive for ≥1 parameter. Results: 426 unrelated patients (age = 64.6 ± 13.0 years; female: male = 113:313) were evaluated. FD was diagnosed in 3 unrelated patients (age = 69.0 ± 3.5 years, female: male = 1:2) and 1 related female subject (age = 43 years). Genetic analyses confirmed the late-onset cardiac variant GLA c.640-801G>A (n = 3) and the missense variant c.869T>C associated with classic FD (n = 1). Cardiac complications were the only significant findings associated with the late-onset c.640-801G>A mutation, manifesting as mild or severe concentric LVH. In contrast, the classic c.869T>C mutation FD exhibited multisystemic manifestations in addition to severe concentric LVH. Conclusions: The prevalence of FD is lower in Chinese patients with LVH when HCM is excluded. The pathological variant c.640-801G>A remains the most common cause of late-onset FD, while the detection of FD in females can be improved by utilizing a gender-specific screening method.
摘要：
背景：法布里病（FD）是一种罕见的X连锁溶酶体贮积症，通常表现为心血管并发症。我们旨在评估中国左心室肥厚（LVH）人群中FD的患病率，同时实施性别特异性筛查方法。方法:LVH患者,定义为左心室间隔/后壁的最大厚度≥13mm，被认为是合格的。排除所有肥厚型心肌病（HCM）患者。使用干血斑点试验评估血浆α-半乳糖苷酶(α-GLA)酶活性。酶活性低的雄性接受了遗传测试以确认FD的诊断，而雌性则进行了α-GLA和球形鞘氨醇浓度的筛查，并且仅在≥1个参数检测为阳性的情况下对GLA基因进行了遗传分析。结果：评估了426例无关患者（年龄=64.6±13.0岁；女性：男性=113：313）。在3例无关患者中诊断出FD（年龄=69.0±3.5岁，女性：男性=1：2）和1名相关女性受试者（年龄=43岁）。遗传分析证实晚发性心脏变异GLAc.640-801G>A（n=3）和错义变异c.869T>C与经典FD（n=1）相关。心脏并发症是与晚发性c.640-801G>A突变相关的唯一重要发现，表现为轻度或重度同心LVH。相比之下,典型的c.869T>C突变FD除了表现为严重的同心LVH外,还表现为多系统表现。结论：排除HCM后，中国LVH患者FD的患病率较低。病理变异c.640-801G>A仍然是迟发型FD的最常见原因，而女性FD的检测可以通过使用性别特异性筛查方法来提高。
