Turkmen Kultigin, Guclu Aydın, Sahin Garip, Kocyigit Ismail, Demirtas Levent, Erdur Fatih Mehmet, Sengül Erkan, Ozkan Oktay, Emre Habib, Turgut Faruk, Unal Hilmi, Karaman Murat, Acıkel Cengiz, Esen Hasan, Balli Ebru, Bıtırgen Gulfidan, Tonbul Halil Zeki, Yılmaz Mahmut Ilker, Ortiz Alberto
Necmettin Erbakan University, Meram School of Medicine, Department of Internal Medicine, Division of Nephrology, Konya, Turkey.
Kidney Blood Press Res. 2016;41(6):1016-1024. doi: 10.1159/000452605. Epub 2016 Dec 23.
BACKGROUND/AIMS: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy.
This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis.
Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever.
The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.
背景/目的:法布里病是慢性肾脏病(CKD)的一个可治疗病因,其特征为α-半乳糖苷酶A基因缺陷。欧洲肾脏最佳实践(ERBP)建议对CKD患者进行法布里病筛查。然而,这是基于专家意见,且尚无关于1 - 5期CKD中法布里病患病率的报道。因此,我们调查了未接受肾脏替代治疗的CKD患者中法布里病的患病率。
这项前瞻性研究评估了313例1 - 5期CKD患者(167例男性)干血斑中的α-半乳糖苷酶活性,这些患者年龄在18 - 70岁之间,CKD病因不明且未接受肾脏替代治疗。通过GLA基因突变分析确诊。
313例CKD患者中有3例(均为男性)被诊断为法布里病,男性患病率为1.80%。家族筛查又发现了8例患有CKD的法布里病患者。在总共11例法布里病患者中,7例为男性并开始接受酶替代治疗,4例为女性。男性患者最常见的表现为疲劳(100%)、耳鸣、眩晕、肢端感觉异常、少汗、角膜涡状浑浊和血管角质瘤(均为85%)、不耐热(71%)以及腹痛(57%)。女性患者最常见的表现为疲劳和角膜涡状浑浊(50%),以及耳鸣、眩晕和血管角质瘤(25%)。3例患者有严重的发作性腹痛和蛋白尿,曾被误诊为家族性地中海热。
在选定的CKD患者中法布里病的患病率与接受肾脏替代治疗的患者中所发现的范围相同,但该病在更早的、可治疗阶段被诊断出来。这些数据支持ERBP对病因不明的CKD患者进行法布里病筛查的建议。