Serebrinsky G, Calvo M, Fernandez S, Saito S, Ohno K, Wallace E, Warnock D, Sakuraba H, Politei J
Labgen, Buenos Aires, Argentina.
Nephrology Department, Hospital Zonal General de Agudos Evita, Buenos Aires, Argentina.
Mol Genet Metab Rep. 2015 Jun 7;4:19-24. doi: 10.1016/j.ymgmr.2015.05.006. eCollection 2015 Sep.
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.
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.
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.
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.
在高危人群中筛查法布里病（FD）会发现大量个体在GLA基因中存在新的超罕见遗传变异，这些个体大多没有FD的典型表现。这些变异通常具有显著的残余α-半乳糖苷酶A活性。确定先前未知或罕见变异的致病特性具有挑战性，但对于指导治疗决策是必要的。
介绍2例有肾脏受累的非典型FD病例，并讨论FD高危人群筛查的重要性。
我们的非典型变异患者是通过透析单位的FD筛查确诊的。然而，器官损伤并不局限于肾脏，因为还存在左心室肥厚、椎基底动脉扩张和角膜涡状浑浊。血浆中溶酶体Gb3浓度处于病理范围，与晚发型FD相符。使用不同工具对p.(Cys174Gly)和p.(Arg363His)进行结构研究和计算机模拟分析表明，酶的不稳定以及可能的聚集可能在器官损伤中起作用。
高危人群的FD筛查项目很重要，因为FD是一种可治疗的多系统疾病，在没有典型表现的患者中经常被忽视。
