COQ2 nephropathy:: A newly described inherited mitochondriopathy with primary renal involvement
COQ2 nephropathy:: A newly described inherited mitochondriopathy with primary renal involvement
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DOI：
10.1681/asn.2006080833
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发表时间：
2007-10-01
影响因子：
13.6
通讯作者：
Emma, Francesco
中科院分区：
文献类型：
--
作者：
Diomedi-Camassei, Francesca;Di Giandomenico, Silvia;Emma, Francesco
原发性辅酶Q（10）（CoQ（10））缺乏症包括一组罕见的常染色体隐性遗传疾病，主要特征是神经和肌肉症状。很少有肾小球受累的报道。COQ 2基因编码辅酶Q（10）合成途径的对羟基苯甲酸-聚异戊二烯基转移酶。我们确定了两名早发性肾小球病变的患者，其COQ 2基因突变。第一个病人在18个月大时因肾小球疾病而出现激素抵抗性肾病综合征，没有肾外症状。第二例患者在出生后5天出现少尿，肾活检显示严重的毛细血管外增生，迅速发展为终末期肾病，并在病程并发进行性癫痫性脑病后6个月时死亡。从这些情况下，以及从两个以前报道的患者肾标本的超微结构检查，显示了肾小球细胞中的异形线粒体数量增加。生化分析表明，呼吸链复合物[II+III]的活动减少，降低辅酶Q（10）在骨骼肌和肾皮质的浓度。总之，我们认为，遗传性辅酶Q2突变引起的原发性肾小球疾病的肾脏病变的严重程度不同，并不一定与神经系统的迹象。当电子显微镜显示足细胞和其他肾小球细胞中异常线粒体数量增加时，应怀疑COQ 2肾病。
Primary coenzyme Q(10) (CoQ(10)) deficiency includes a group of rare autosomal recessive disorders primarily characterized by neurological and muscular symptoms. Rarely, glomerular involvement has been reported. The COQ2 gene encodes the para-hydroxybenzoate-polyprenyl-transferase enzyme of the CoQ(10) synthesis pathway. We identified two patients with early-onset glomerular lesions that harbored mutations in the COQ2 gene. The first patient presented with steroid-resistant nephrotic syndrome at the age of 18 months as a result of collapsing glomerulopathy, with no extrarenal symptoms. The second patient presented at five days of life with oliguria, had severe extracapillary proliferation on renal biopsy, rapidly developed end-stage renal disease, and died at the age of 6 months after a course complicated by progressive epileptic encephalopathy. Ultrastructural examination of renal specimens from these cases, as well as from two previously reported patients, showed an increased number of dysmorphic mitochondria in glomerular cells. Biochemical analyses demonstrated decreased activities of respiratory chain complexes [II+III] and decreased CoQ(10) concentrations in skeletal muscle and renal cortex. In conclusion, we suggest that inherited COQ2 mutations cause a primary glomerular disease with renal lesions that vary in severity and are not necessarily associated with neurological signs. COQ2 nephropathy should be suspected when electron microscopy shows an increased number of abnormal mitochondria in podocytes and other glomerular cells.