Li Ting, Lu Zhihong, Wang Jingjing, Chen Junyi, Fu Haidong, Mao Jianhua
Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, 3333 Binsheng Road, Hangzhou 310052, China.
Children (Basel). 2021 Oct 4;8(10):887. doi: 10.3390/children8100887.
Fanconi syndrome is one of the primary renal manifestations of mitochondrial cytopathies caused by mitochondrial DNA (mtDNA) mutation. The common 4977-bp mtDNA deletion has been reported to be associated with aging and diseases involving multiple extrarenal organs. Cases of Fanconi syndrome caused by the 4977-bp deletion were rarely reported previously. Here, we report a 6-year-old girl with growth retardation in the course of Fanconi syndrome. She had mild ptosis and pigmented retinopathy. Abnormal biochemical findings included low-molecular-weight proteinuria, normoglycemic glycosuria, increased urine phosphorus excretion, metabolic acidosis, and hypophosphatemia. Growth records showed that her body weight and height were normal in the first year and failed to thrive after the age of three. Using a highly sensitive mtDNA analysis methodology, she was identified to possess the common 4977-bp mtDNA deletion. The mutation rate was 84.7% in the urine exfoliated cells, 78.67% in the oral mucosal cells, and 23.99% in the blood sample. After three months of oral coenzyme Q10 and levocarnitine treatment in combination with standard electrolyte supplement, her condition was improved. This is a report of growth retardation as the initial major clinical presentation of Fanconi syndrome caused by the deletion of the 4977-bp fragment. Renal tubular abnormality without any other extrarenal dysfunction may be an initial clinical sign of mitochondrial disorders. Moreover, considering the heterogeneity of the phenotypes associated with mtDNA mutations, the risk of developing Kearns-Sayre syndrome (KSS) with age in this patient should be noted because she had ptosis, retinal involvement, and changes in the brain and skeletal muscle.
范科尼综合征是由线粒体DNA(mtDNA)突变引起的线粒体细胞病的主要肾脏表现之一。据报道,常见的4977碱基对mtDNA缺失与衰老及涉及多个肾外器官的疾病有关。此前,由4977碱基对缺失引起的范科尼综合征病例鲜有报道。在此,我们报告一名6岁患有范科尼综合征且生长发育迟缓的女孩。她有轻度上睑下垂和色素性视网膜病变。异常生化检查结果包括低分子量蛋白尿、血糖正常性糖尿、尿磷排泄增加、代谢性酸中毒和低磷血症。生长记录显示,她第一年体重和身高正常,3岁后发育不良。采用高灵敏度的mtDNA分析方法,确定她存在常见的4977碱基对mtDNA缺失。尿脱落细胞中的突变率为84.7%,口腔黏膜细胞中的突变率为78.67%,血样中的突变率为23.99%。在口服辅酶Q10和左卡尼汀治疗三个月并结合标准电解质补充后,她的病情有所改善。这是一篇关于因4977碱基对片段缺失导致范科尼综合征以生长发育迟缓为最初主要临床表现的报告。无任何其他肾外功能障碍的肾小管异常可能是线粒体疾病的初始临床征象。此外,考虑到与mtDNA突变相关表型的异质性,应注意该患者随年龄增长发生凯-塞尔综合征(KSS)的风险,因为她有上睑下垂、视网膜受累以及脑和骨骼肌的改变。