Citro Rodolfo, Prota Costantina, Ferraioli Donatella, Iuliano Giuseppe, Bellino Michele, Radano Ilaria, Silverio Angelo, Migliarino Serena, Polito Maria Vincenza, Ruggiero Artemisia, Napoletano Rosa, Bellizzi Vincenzo, Ciccarelli Michele, Galasso Gennaro, Vecchione Carmine
Heart Department, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.
Vascular Physiopathology Unit, Department of Angio-Cardio-Neurology, IRCCS Neuromed, Pozzilli, Italy.
Front Cardiovasc Med. 2022 Apr 25;9:838200. doi: 10.3389/fcvm.2022.838200. eCollection 2022.
Aim of this study was to evaluate, in a metropolitan area not already explored, the prevalence of Anderson-Fabry disease, by genetic screening, in patients with echocardiographic evidence of left ventricular hypertrophy (LVH) of unknown origin and "clinical red flags".
From August 2016 to October 2017, all consecutive patients referring to our echo-lab for daily hospital practices with echocardiographic evidence of LVH of unknown origin in association with history of at least one of the classical signs and symptoms related to Fabry disease (FD) (neuropathic pain, anhidrosis/hypohidrosis, angiokeratomas, gastrointestinal problems, chronic kidney disease, or cerebrovascular complications) were considered eligible for the FD genetic screening program. Through dried blood spot testing, α-Galactosidase A (α-Gal A) activity and analysis of the gene were performed.
Among 3,360 patients who underwent transthoracic echocardiography in our echo-lab during the study period, 30 patients (0.89%; 19 men, mean age 58 ± 18.2 years) were selected. FD was diagnosed in 3 (10%) unrelated patients. Three different gene mutations were detected, one of them [mutation c.388A > G (p.Lys130Glu) in exon 3] never described before. Moreover, probands' familiar genetic screening allowed the identification of 5 other subjects affected by FD.
In a metropolitan area not previously investigated, among patients with LVH of unknown origin associated with other "red flags," undergoing genetic screening, the prevalence of FD was very high (10%). Our results highlight the importance of an echocardiographic- and clinical-oriented genetic screening for FD in patients with uncommon cause of LVH.
本研究的目的是，在一个尚未进行过探索的大都市地区，通过基因筛查，评估不明原因左心室肥厚（LVH）且有“临床警示信号”的患者中安德森 - 法布里病的患病率。
从2016年8月至2017年10月，所有因日常医院诊疗前来我们超声心动图实验室，有不明原因LVH且伴有至少一项与法布里病（FD）相关的典型体征和症状（神经性疼痛、无汗/少汗、血管角质瘤、胃肠道问题、慢性肾病或脑血管并发症）病史的连续患者，被认为符合FD基因筛查项目的条件。通过干血斑检测，进行α - 半乳糖苷酶A（α - Gal A）活性和基因分析。
在研究期间于我们超声心动图实验室接受经胸超声心动图检查的3360例患者中，挑选出30例患者（0.89%；19名男性，平均年龄58 ± 18.2岁）。3例（10%）无血缘关系的患者被诊断为FD。检测到三种不同的基因突变，其中一种（外显子3中的突变c.388A > G（p.Lys130Glu））此前从未被描述过。此外，先证者的家族基因筛查还发现了另外5名受FD影响的个体。
在一个此前未进行过调查的大都市地区，在不明原因LVH且伴有其他“警示信号”并接受基因筛查的患者中，FD的患病率非常高（10%）。我们的结果突出了对罕见病因LVH患者进行以超声心动图和临床为导向的FD基因筛查的重要性。
