Department of Nephrology, Centro Hospitalar de São João, Porto, Portugal; Group of Research and Development in Nephrology and Infectious Diseases, Institute of Biomedical Engineering-I(3)S, University of Porto, Porto, Portugal.
Group of Research and Development in Nephrology and Infectious Diseases, Institute of Biomedical Engineering-I(3)S, University of Porto, Porto, Portugal; Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.
Am J Kidney Dis. 2017 Aug;70(2):235-243. doi: 10.1053/j.ajkd.2017.01.048. Epub 2017 Mar 27.
Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases.
Case series.
SETTING & PARTICIPANTS: 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members.
Kidney disease, kidney disease progression, and survival.
The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis.
Retrospective data collection for patients with amyloidosis previously diagnosed.
AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent.
纤维蛋白原 Aα 链（AFib）淀粉样变性是由编码 AFib（FGA）的基因中的常染色体显性突变引起的。患有这种疾病的患者通常表现为蛋白尿。在葡萄牙西北部布拉加地区发现了携带 FGA p.Glu545Val 变异的孤立 AFib 淀粉样变性病例。这一观察结果使我们假设，这种疾病可能是该地区未被识别的肾脏疾病的一个原因，并促使我们对当地血液透析患者和已确诊病例的家族成员进行针对 p.Glu545Val 变异的靶向基因检测。
病例系列。
3 组参与者：（1）肾脏活检登记处，n=4；（2）血液透析中心，n=267 名患者中的 122 名；（3）遗传风险个体；n=167 名家族成员中的 69 名。
在活检登记处的 4 名患者中均发现了 p.Glu545Val 变异，在 122 名接受检测的血液透析患者中发现了 12 名（9.8%），在 69 名接受检测的亲属中发现了 34 名（49%）。这 50 例属于 13 个无关家庭，61%的先证者患有肾脏疾病或淀粉样变性。35 名个体在 51.0±10.4 岁时出现高血压。其中 30 名在 56.7±12.0 岁时出现肾脏疾病，21 名在 61.4±11.3 岁时开始透析治疗。随着疾病的进展，心脏、肝脏、脾脏、结肠和回肠都受到了影响。在接受血液透析的 AFib 淀粉样变性患者中，有 25%的患者以前曾将肾脏疾病归因于高血压。
对以前诊断为淀粉样变性的患者进行回顾性数据收集。
AFib 淀粉样变性在葡萄牙布拉加似乎是一种未被充分认识的疾病，我们发现 FGA p.Glu545Val 变异的频率很高。由于其主要临床特征的非特异性性质，AFib 淀粉样变性的诊断应高度怀疑，特别是在高血压流行的人群中。
