童年期发病的Leber遗传性视神经病变临床研究

A clinical study of childhood-onset Leber's hereditary optic ueuropathy

目的探讨童年期发病的Leber遗传性视神经病变(LHON)患者线粒体DNA(mtDNA)突变的主要类型、临床特征及预后。方法 2000年6月—2015年6月在我院眼科就诊且经实验室检查已确诊为LHON的患者279例,对其中≤16岁的童年期发病LHON患者共计161例进行临床资料归纳分析。结果 161例童年期发病LHON中11778位点突变者144例(89.4%),其中3例合并14502位点突变,1例合并11696位点突变,1例合并14693位点突变。14484位点突变者11例(6.8%),继发位点突变6例(3.7%),其中3316位点突变2例,14693位点突变2例,11696位点突变1例,3497位点突变1例。未检测到3460等其他常见原发突变位点。童年期发病LHON典型临床表现为:双眼先后或同时中心视力急性或缓慢下降,多不伴眼球疼痛,视野检查以中心或旁中心暗点为主。随访视力恢复至≥0.3的儿童LHON患者中,11778位点突变者104只眼中有13只眼,占12.5%,14484位点突变者6只眼中有4只眼,占66.7%。童年期发病的LHON患儿中部分低年龄段儿童初诊视力及最终视力恢复比大龄儿童好。结论童年期发病LHON患儿其主要突变位点发生率及临床特征与成人LHON患者相似,其中部分低年龄段儿童视力恢复较好。童年期发病LHON患者应与其他遗传性视神经疾病及儿童视神经炎相鉴别。

OBJECTIVE To investigate the main mitochondfial DNA （mtDNA） mutation types, clinical char- acteristics and the prognosis of Leber＇s Hereditary Optic Neuropathy （LHON） onset in childhood. METHODS A total of 161 cases with childhood-onset LHON aged 16 years or younger were selected from 279 cases and then ana- lyzed, all of whom were diagnosed with laboratory proof. RESULTS Among the 161 cases, G11778A primary muta- tion occurred in 144 cases （89.4%）, while 3 of them was complicated with 14502 mt-DNA mutations, 1 of them with 11696 mt-DNA mutation in addition, and 1 of them was accompanied with the 14693 mt-DNA mutation. And G14484A primary mutation occurred in 11 cases （6.8%）. Besides, 6 cases （3.7%） were identified with secondary mutations, among which 2 cases were of 3316 mt-DNA mutation, 2 cases were of 14693 mt-DNA mutation, 1 case was of 11696 mt-DNA mutation and 1 case was of 3497 mt-DNA mutation. However, some classic primary muta- tions such as 3460 mutation were not found. Childhood-onset LHON typically manifested symptoms and signs as ： a- cute or subacute painlessly central vision loss in both eyes at the same time or one eye after another; a central or para-central scotoma in visual field test. In this study, 13 eyes （12.5%） of 104 with G11778A mutation and 4 eyes （66.7%） of 6 with G14484A mutation restored visual acuity to 0.3 or better. In addition, younger cases showed bet- ter restorative visual acuity than elder cases both in initial and follow-up test. CONCLUSIONS The main mt-DNA mutation types and clinical characteristics of childhood-onset LI-ION patients were similar with adult-onset patients. Onset in younger age often implied lower damage and better prognosis. The childhood-onset LHON should be differentiated from other hereditary optic neuropathy and children optic neuritis.