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Abstract：
BACKGROUND: Screening for Fabry disease (FD) in high risk populations yields a significant number of individuals with novel, ultra rare genetic variants in the GLA gene, largely without classic manifestations of FD. These variants often have significant residual α-galactosidase A activity. The establishment of the pathogenic character of previously unknown or rare variants is challenging but necessary to guide therapeutic decisions.
OBJECTIVE: To present 2 cases of non-classical presentations of FD with renal involvement as well as to discuss the importance of high risk population screenings for FD.
RESULTS: Our patients with non-classical variants were diagnosed through FD screenings in dialysis units. However, organ damage was not limited to kidneys, since LVH, vertebrobasilar dolichoectasia and cornea verticillata were also present. Lyso-Gb3 concentrations in plasma were in the pathologic range, compatible with late onset FD. Structural studies and in silico analysis of p.(Cys174Gly) and p.(Arg363His), employing different tools, suggest that enzyme destabilization and possibly aggregation could play a role in organ damage.
CONCLUSIONS: Screening programs for FD in high risk populations are important as FD is a treatable multisystemic disease which is frequently overlooked in patients who present without classical manifestations.
OBJECTIVE: To present 2 cases of non-classical presentations of FD with renal involvement as well as to discuss the importance of high risk population screenings for FD.
RESULTS: Our patients with non-classical variants were diagnosed through FD screenings in dialysis units. However, organ damage was not limited to kidneys, since LVH, vertebrobasilar dolichoectasia and cornea verticillata were also present. Lyso-Gb3 concentrations in plasma were in the pathologic range, compatible with late onset FD. Structural studies and in silico analysis of p.(Cys174Gly) and p.(Arg363His), employing different tools, suggest that enzyme destabilization and possibly aggregation could play a role in organ damage.
CONCLUSIONS: Screening programs for FD in high risk populations are important as FD is a treatable multisystemic disease which is frequently overlooked in patients who present without classical manifestations.
摘要：
背景：在高危人群中筛查法布里病（FD）会产生大量新的个体，GLA基因中非常罕见的遗传变异，在很大程度上没有FD的经典表现。这些变体通常具有显著的残余α-半乳糖苷酶A活性。建立以前未知或罕见的变异的致病特征是具有挑战性的，但对于指导治疗决策是必要的。
目的：介绍2例非经典FD合并肾脏受累的病例，并讨论对FD进行高危人群筛查的重要性。
结果：我们的非经典变异型患者是通过透析单位的FD筛查来诊断的。然而,器官损伤不仅限于肾脏，自从LVH,还出现了椎基底动脉扩张和角膜。血浆中的Lyso-Gb3浓度在病理范围内，与迟发性FD相容。p的结构研究和计算机模拟分析。（Cys174Gly）和p。（Arg363His），使用不同的工具，表明酶不稳定和可能的聚集可能在器官损伤中起作用。
结论：在高危人群中进行FD筛查是重要的，因为FD是一种可治疗的多系统疾病，在没有经典表现的患者中经常被忽视。
目的：介绍2例非经典FD合并肾脏受累的病例，并讨论对FD进行高危人群筛查的重要性。
结果：我们的非经典变异型患者是通过透析单位的FD筛查来诊断的。然而,器官损伤不仅限于肾脏，自从LVH,还出现了椎基底动脉扩张和角膜。血浆中的Lyso-Gb3浓度在病理范围内，与迟发性FD相容。p的结构研究和计算机模拟分析。（Cys174Gly）和p。（Arg363His），使用不同的工具，表明酶不稳定和可能的聚集可能在器官损伤中起作用。
结论：在高危人群中进行FD筛查是重要的，因为FD是一种可治疗的多系统疾病，在没有经典表现的患者中经常被忽视。
