辅酶Q10治疗COQ6基因突变致肾病一例并文献复习

Coenzyme Q10 treatment for one child with COQ6 gene mutation induced nephrotic syndrome and literature review

目的总结COQ6基因突变致辅酶Q肾病的临床特征、分子生物学特点及治疗疗效。方法分析2015年6月复旦大学附属儿科医院肾脏风湿科收治的1例临床确诊为COQ6基因突变致辅酶Q肾病的病史特点，实验室检查和家族史等资料。给予辅酶Q1030mg／（kg·d）治疗，测定尿蛋白／肌酐（mg/mg），血白蛋白，血肌酐等指标以评价其疗效。并进行相关文献复习。结果（1）患儿男，10月龄，出生后发现心脏杂音，伴生长发育落后、左眼睑下垂和四肢肌张力低下，10月龄时检查发现存在蛋白尿，不伴水肿；24h尿蛋白1．04g，尿蛋白／肌酐7．2，白蛋白22．5g／L，肌酐14．0μmol/L。非近亲家族。基因检测到COQ6基因的纯合p．R360W错义突变，为新发现的突变。患儿父母分别携带杂合P．R360W错义突变。经在线软件PolyPhen和SIFT预测，COQ6基因P．R360W错义突变为有害性突变。行辅酶Q10治疗2个月后，尿蛋8／肌酐1．3，血白蛋白36．1g／L；治疗至3个月尿蛋白／肌酐0．01，肾病达到完全缓解；随访至治疗后12个月，出现单侧感应神经性耳聋，肾病仍维持缓解，肾功能正常，精神运动发育改善。（2）全球报道7个家系13例COQ6基因突变致肾病病例，表现为6种不同的基因突变类型。均表现为激素耐药型肾病综合征，有肾活检资料的8例：局灶节段肾小球硬化7例，弥漫系膜硬化性肾炎1例。伴有感音神经性耳聋9例，共济失调和面部畸形2例，伴惊厥2例，伴脑白质异常、肾石症和发育迟滞各1例。4例接受了辅酶Q10补充治疗，显示不同程度的疗效。结论COQ6基因突变所致的肾脏病变表现为肾病综合征。早期辅酶Q10补充治疗有效，肾病可达到完全缓解。

Objective To summarize the clinical manifestation and molecular characteristics of COQ6 mutation induced nephrotic syndrome, and to evaluate efficacy of CoQ10 therapy. Method Clinical data of the case with infantile nephrotic syndrome was summarized, including clinical manifestations, laboratory findings and family investigation. The patient received CoQ10 30 rag/（ kg · d） therapy. Urine protein/creatinine ratio, serum albumin and creatinine were detected to assess the efficacy of the therapy. Result （1） The 10 months old boy was presented with nephrotic level proteinuria and hypoalbuminemia. Extra-renal manifestations included cardiovascular abnormality, motor and mental retardation and unilateral ptosis. The patient had no consanguinity. A novel homozygous p. R360W mutation in COQ6 gene was identified and confirmed by next-generation sequencing and Sanger sequencing, respectively. Family analysis showed that homozygous p. R360W mutation in COQ6 gene was inherited from his parents. Missense p. R360W mutation was damaging by prediction online PolyPhen and SIFT software. After 2 months of CoQ10 complementary therapy, the patient＇s urine protein/creatinine ratio declined from 7. 2 to 1.3, and decreased further to 0. 01 mg/mg with normal albumin level and renal function within 3 months. Nephropathy remission was maintained and growth retardation improved significantly during the last follow-up. Nevertheless, the patient manifested with sensorineural deafness at the age of 2 years. （2） There were 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 （COQ6） in 13 individuals from 7 families by homozygosity mapping in the whole world. Each mutation was linked to early-onset SRNS with sensorineural deafness. Renal biopsy revealed FSGS in 7 cases and DMS in 1 case. Other manifestations included ataxia, seizures, facial dysmorphism, nephrolithiasis and growth retardation. Four patients received CoQ10 supplementation and responded to the treatment. Conclusion Renal disease caused by recessive COQ6 gene mutation was nephrotic syndrome. The patient benefited from early CoQm0 complement and reached nephropathy remission.