Yılmaz M, Uçar S K, Aşçı G, Canda E, Tan F A, Hoşcoşkun C, Çoker M, Töz H
Department of Nephrology, Ege University, School of Medicine, Izmir, Turkey.
Department of Pediatric Metabolism and Nutrition, Ege University, School of Medicine, Izmir, Turkey.
Transplant Proc. 2017 Apr;49(3):420-424. doi: 10.1016/j.transproceed.2017.01.025.
Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of alfa-galactosidase A (AGALA) and leads to progressive impairment of renal function in almost all male patients and in a significant proportion of female patients. FD is underdiagnosed or even misdiagnosed in patients undergoing kidney transplantation. We initiated a selective screening study for FD among kidney transplant patients in our center. In this study, 1095 male and female patients were included. Dried blood samples on Guthrie papers were used to analyze galactosidase A enzyme for male patients. Genetic analyses were performed in all female and male patients with low enzyme activity. In total, 648 female and 447 male patients with functioning grafts were evaluated. Among 1095 patients, 5 male patients had AGALA activity below threshold and 3 female patients had galactosidase alpha gene DNA variations. One male patient had a disease-causing mutation. The other 4 patients had polymorphisms causing low enzyme activity. All the 3 female patients had mutations that were associated with FD according to Human Gene Mutation Database (ID: CM025441). In contrast, these mutations were reported as unknown clinical significance in Clinvar (rs149391489). The patients with clinical findings suggesting FD were planned to be analyzed for Lyso Gb3. In our selective screening study, 8 variations were found among 1095 kidney transplantation patients, which needs further investigation to determine causes of FD. Clinical findings, physical examination, and family history are also necessary to evaluate the genetic changes as a mutation in this selected population.
法布里病（FD）是一种罕见的X连锁溶酶体贮积症，由α-半乳糖苷酶A（AGALA）缺乏引起，几乎所有男性患者以及相当比例的女性患者都会出现进行性肾功能损害。在接受肾移植的患者中，FD常被漏诊甚至误诊。我们在本中心开展了一项针对肾移植患者的FD选择性筛查研究。该研究纳入了1095名男性和女性患者。使用滤纸片上的干血样分析男性患者的半乳糖苷酶A酶活性。对所有酶活性低的女性和男性患者进行基因分析。总共评估了648名女性和447名移植肾功能正常的男性患者。在1095名患者中，5名男性患者的AGALA活性低于阈值，3名女性患者的半乳糖苷酶α基因存在DNA变异。1名男性患者存在致病突变。其他4名患者的多态性导致酶活性降低。根据人类基因突变数据库（ID：CM025441），所有3名女性患者的突变均与FD相关。相比之下，这些突变在Clinvar（rs149391489）中被报告为临床意义不明。对有提示FD临床表现的患者计划进行溶酶体Gb3分析。在我们的选择性筛查研究中，1095名肾移植患者中发现了8种变异，这需要进一步研究以确定FD的病因。在这个特定人群中评估基因变化作为一种突变时，临床表现、体格检查和家族史也很有必要。
