Narumi Kaori, Mishima Eikan, Akiyama Yukako, Matsuhashi Tetsuro, Nakamichi Takashi, Kisu Kiyomi, Nishiyama Shuhei, Ikenouchi Hajime, Kikuchi Akio, Izumi Rumiko, Miyazaki Mariko, Abe Takaaki, Sato Hiroshi, Ito Sadayoshi
Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
Nephron. 2018;138(3):243-248. doi: 10.1159/000485109. Epub 2017 Nov 30.
Focal segmental glomerulosclerosis (FSGS) is caused by various etiologies, with mitochondrial dysfunction being one of the causes. FSGS is known to be associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), which is a subclass of mitochondrial disease. However, it has rarely been reported in other mitochondrial disease subclasses. Here, we reported a 20-year-old man diagnosed with FSGS associated with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA (mtDNA) 3243A>G mutation. He presented with left ptosis, short stature, mild sensorineural deafness, and cardiac conduction block. A renal biopsy sample showed segmental sclerosis and adhesions between capillaries and Bowman's capsule, indicating FSGS. Electron microscopy demonstrated abnormal aggregated mitochondria in podocytes, and the basement membrane and epithelial cells of Bowman's capsule. Skeletal muscle biopsy also showed accumulation of abnormal mitochondria. mtDNA analysis identified heteroplasmic mtDNA 3243A>G mutation with no large-scale deletions. From these findings, we diagnosed the case as CPEO with multi-organ involvement including FSGS. Our report demonstrates that CPEO, as well as MELAS, can be associated with FSGS. Because mitochondrial disease presents with a variety of clinical symptoms, atypical cases with non-classical manifestations are observed. Thus, mitochondrial disease should be considered as an underlying cause of FSGS with systemic manifestations even with atypical phenotypes.
局灶节段性肾小球硬化（FSGS）由多种病因引起，线粒体功能障碍是其中之一。已知FSGS与线粒体脑肌病、乳酸酸中毒和卒中样发作（MELAS）相关，MELAS是线粒体疾病的一个亚类。然而，在其他线粒体疾病亚类中很少有相关报道。在此，我们报告了一名20岁男性，诊断为因线粒体DNA（mtDNA）3243A>G突变导致的与慢性进行性眼外肌麻痹（CPEO）相关的FSGS。他表现为左眼睑下垂、身材矮小、轻度感音神经性耳聋和心脏传导阻滞。肾活检样本显示节段性硬化以及毛细血管与鲍曼囊之间的粘连，提示FSGS。电子显微镜检查显示足细胞以及鲍曼囊的基底膜和上皮细胞中有异常聚集的线粒体。骨骼肌活检也显示有异常线粒体的积聚。mtDNA分析鉴定出异质性mtDNA 3243A>G突变，无大规模缺失。根据这些发现，我们将该病例诊断为CPEO伴多器官受累，包括FSGS。我们的报告表明，CPEO以及MELAS都可能与FSGS相关。由于线粒体疾病表现出多种临床症状，会观察到具有非典型表现的不典型病例。因此，即使具有非典型表型，线粒体疾病也应被视为具有全身表现的FSGS的潜在病因。
