背景:法布里病是一种多系统疾病,其特征是在多个器官中沉积了球形三甲神经酰胺(Gb3)及其脱酰基形式,有时局限于特定系统,如神经或心血管系统。由于现在可以使用疾病修饰疗法,早期诊断对于改善生活质量和临床结局至关重要.尽管广泛使用非侵入性技术来评估器官损伤,例如心脏病患者的心脏磁共振成像(MRI),器官活检仍是评估器官受累的金标准.
方法:2例患者,患有W162C突变的父亲和女儿,被描述。父亲出现了迟发性,心脏病法布里病,随后发展为收缩功能障碍和心力衰竭。他的女儿,虽然无症状且心脏评估正常(除了心脏MRI轻微降低的自然T1值),心内膜活检上已经有最初的肌细胞Gb3沉积,让她早熟地开始治疗,并有可能改变她的病程。然后提供有关W162C突变的文献综述,表明它通常与经典相关,多系统法布里病,而不是这两种情况下的心脏限制性形式。
结论:从本报告可以得出三个主要观点。首先,W162C突变可以呈现比分子基础上预测的更多样化的表型。第二,在这种情况下,心内膜活检显示在确定器官受累的非侵入性检查之前,证明对这种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。
BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: 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.