IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Via Altura 3, 40139, Bologna, Italy.
Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
BMC Neurol. 2024 Apr 5;24(1):113. doi: 10.1186/s12883-024-03540-3.
Fabry disease is a multisystemic disorder characterized by deposition of globotriaosylceramide (Gb3) and its deacylated form in multiple organs, sometimes localized in specific systems such as the nervous or cardiovascular system. As disease-modifying therapies are now available, early diagnosis is paramount to improving life quality and clinical outcomes. Despite the widespread use of non-invasive techniques for assessing organ damage, such as cardiac magnetic resonance imaging (MRI) for patients with cardiac disease, organ biopsy remains the gold standard to assess organ involvement.
The cases of two patients, father and daughter with a W162C mutation, are described. The father presented with late-onset, cardiac Fabry disease, subsequently developing systolic dysfunction and heart failure. His daughter, while asymptomatic and with normal cardiac assessment (except for slightly reduced native T1 values by cardiac MRI), had already initial myocyte Gb3 deposits on the endomyocardial biopsy, allowing her to start therapy precociously and potentially modifying the course of her disease. A review of the literature concerning the W162C mutation is then provided, showing that it is usually associated to classic, multisystemic Fabry disease rather than the cardiac-restricted form as in these two cases.
Three main points can be concluded from this report. First, the W162C mutation can present with a more variegate phenotype than that predicted on a molecular basis. Second, endomyocardial biopsy was shown in this case to precede non-invasive investigation in determining organ involvement, justifying further studies on this potentially reliable technique, Third, difficulties can arise in the management of asymptomatic female carriers.
法布瑞氏病是一种多系统疾病，其特征是在多个器官中沉积神经酰胺三己糖苷（Gb3）及其去酰基形式，有时局部定位于特定系统，如神经系统或心血管系统。由于现在有了可改变疾病进程的治疗方法，早期诊断对于提高生活质量和临床结局至关重要。尽管现在广泛使用心脏磁共振成像（MRI）等非侵入性技术来评估心脏疾病患者的器官损伤，但器官活检仍然是评估器官受累的金标准。
描述了两位携带 W162C 突变的患者，即父女的病例。父亲表现为迟发性心脏法布瑞氏病，随后出现收缩功能障碍和心力衰竭。他的女儿无症状，心脏评估正常（除心脏 MRI 显示略有降低的原生 T1 值外），但已经在心内膜心肌活检中出现了初始心肌 Gb3 沉积，这使她能够及早开始治疗，并可能改变疾病进程。然后对有关 W162C 突变的文献进行了综述，表明该突变通常与经典的多系统法布瑞氏病相关，而不是像这两个病例中的心脏受限形式。
从本报告中可以得出三个主要结论。首先，W162C 突变的表型可能比基于分子基础预测的更为多样化。其次，在确定器官受累方面，心内膜心肌活检先于非侵入性检查，证明了该潜在可靠技术的进一步研究是合理的。第三，无症状女性携带者的管理可能会出现困难。
