Doleris L M, Hill G S, Chedin P, Nochy D, Bellanne-Chantelot C, Hanslik T, Bedrossian J, Caillat-Zucman S, Cahen-Varsaux J, Bariety J
Department of Internal Medicine and Nephrology, Hôpital A. Paré, Boulogne Billancourt, France.
Kidney Int. 2000 Nov;58(5):1851-8. doi: 10.1111/j.1523-1755.2000.00356.x.
The nonspecific lesion of focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. In mitochondrial cytopathies (MCs), the phenotypic expression of the disease depends on the degree of cellular dysfunction, and this correlates with the proportion of abnormal mitochondrial DNA in the cells and the dependence of tissues on oxidative metabolism. The most common renal manifestation in MCs is tubular dysfunction; little has been reported about glomerular diseases.
Cases of four adult patients with FSGS and MC are reported. Routine histology and mitochondrial DNA analysis were carried out on renal biopsies.
Family history and clinical manifestations in the four patients with FSGS suggested a diagnosis of MC. An A3243G transition in the mitochondrial DNA tRNA(leu(UUR)) was found in lymphocytes and kidney. Glomerular lesions of FSGS were associated with unusual hyaline lesions, which appeared to represent individual myocyte necrosis in afferent arterioles and small arteries.
FSGS is a renal manifestation of MCs. The renal lesion can precede other manifestations of the genetic disease by many years. The striking arteriolar lesions in these cases may have resulted in glomerular hypertension and hyperperfusion, leading to secondary epithelial cell abnormalities and, ultimately, FSGS. However, primary epithelial cell dysfunction caused by mitochondrial defects could not be ruled out on morphological grounds. MCs should be considered in cases of so-called primary FSGS, particularly if there is a familial history of diabetes, neuromuscular disorders, or deafness.
局灶节段性肾小球硬化（FSGS）的非特异性病变可作为原发性疾病出现，也可出现在多种继发性情况下。在线粒体细胞病（MCs）中，疾病的表型表达取决于细胞功能障碍的程度，这与细胞中异常线粒体DNA的比例以及组织对氧化代谢的依赖性相关。MCs中最常见的肾脏表现是肾小管功能障碍；关于肾小球疾病的报道较少。
报告了4例成年FSGS合并MC患者的病例。对肾活检组织进行常规组织学和线粒体DNA分析。
4例FSGS患者的家族史和临床表现提示为MC诊断。在淋巴细胞和肾脏中发现线粒体DNA tRNA(leu(UUR))存在A3243G转换。FSGS的肾小球病变与不寻常的玻璃样病变相关，这些病变似乎代表入球小动脉和小动脉中的单个肌细胞坏死。
FSGS是MCs的肾脏表现。肾脏病变可能比该遗传病的其他表现提前多年出现。这些病例中显著的小动脉病变可能导致肾小球高血压和高灌注，进而导致继发性上皮细胞异常，最终发展为FSGS。然而，基于形态学原因不能排除线粒体缺陷导致的原发性上皮细胞功能障碍。在所谓的原发性FSGS病例中应考虑MCs，特别是如果有糖尿病、神经肌肉疾病或耳聋的家族史。
