成年期巨蛋白缺乏症的肾脏病理

文献信息

中文摘要

巨蛋白属于大型低密度脂蛋白受体相关蛋白亚家族，在经肾小球滤器自由滤过的低分子量蛋白的肾小管重吸收中起关键作用。巨蛋白缺乏症是一种超罕见遗传病（面-眼-听-肾综合征或Donnay-Barrow综合征），多在儿童期诊断。在本研究中，我们报告一例罕见的双等位基因LRP2突变病例，LRP2是编码内吞受体巨蛋白的基因，患者为一名51岁女性，表现为慢性肾脏病（CKD）伴不完全性近端小管功能障碍、中度感音神经性听力损失、重度近视和会聚性斜视。肾活检显示轻度间质纤维化伴肾小管萎缩，但存在严重肾小球硬化。其他CKD病因已被排除。本病例突出以下方面：（1）尽管巨蛋白主要被认为是近端小管生理的关键因子，但巨蛋白缺乏在人类中与以肾小球瘢痕病变为主相关，促进类似小鼠模型的缓慢进展性CKD；（2）巨蛋白可参与足细胞生理；（3）LRP2应纳入用于评估不明原因肾病的肾脏基因panel，即使在成年期也应如此。

英文摘要

Megalin belongs to the large low-density lipoprotein receptor--related protein subfamily and is pivotal in the tubular reabsorption of low-molecular-weight proteins freely filtered through the glomerular filter. Megalin deficiency is an ultrarare inherited disease (faciooculoacousticorenal or Donnay-Barrow syndrome) mostly diagnosed in childhood. In this study, we report an exceptional case of biallelic mutations in LRP2, the gene encoding the endocytic receptor megalin, diagnosed in a 51-year-old woman and characterized by chronic kidney disease (CKD) with incomplete proximal tubule dysfunction, moderate sensorineural hearing loss, severe myopia, and convergent strabismus. Kidney biopsy showed mild interstitial fibrosis with tubular atrophy but severe glomerulosclerosis. Other causes of CKD were ruled out. This case highlights the following aspects: (1) although megalin is mainly recognized as a key factor of proximal tubule physiology, megalin deficiency was associated with predominantly glomerular scarring lesions in humans, promoting slowly progressive CKD similar to mouse models; (2) megalin can contribute to podocyte physiology; and (3) LRP2 should be included in kidney gene panels for the evaluation of nephropathy of unknown origin, even in adulthood.