生酮饮食治疗TBC1D24基因相关婴儿癫痫伴游走性局灶性发作二例并文献复习

Ketogenic diet therapy in the epilepsy of infancy with migrating focal seizures associated with TBC1D24 gene mutation: two case reports and literature review

目的探讨生酮饮食治疗TBC1D24基因相关婴儿癫痫伴游走性局灶性发作(EIMFS)的疗效与安全性。方法回顾性收集2019—2020年就诊于福建医科大学附属协和医院儿科的2例TBC1D24基因相关EIMFS患儿的临床资料,总结其临床特点及生酮饮食治疗情况,并进行文献复习。结果2例癫痫患儿均在6月龄前发病,表现为多灶性的局部肌阵挛发作、癫痫持续状态,临床发作频繁,伴有明显的精神运动发育落后。发作间期脑电图可见少量局灶性尖波、棘波、尖慢复合波、棘慢复合波发放。基因检测结果为TBC1D24基因突变,1例为复合杂合突变(c.1025C>T,p.S342L;c.229_c.240delATCGTGGGCAAG,p.I77_K80del),1例为纯合突变[c.119G>A,p.R40H(Arg40His)]。2例患儿经多种抗癫痫药物治疗效果不佳,为药物难治性癫痫。生酮饮食治疗4~17个月后,癫痫得到有效控制,未出现明显不良反应。通过文献复习,发现在6例TBC1D24基因相关EIMFS患儿中,4例经生酮饮食治疗有效或部分有效,1例因生酮比例不足而中止,1例未见明显效果而中止,均无明显不良反应。结论TBC1D24基因相关EIMFS多为药物难治性癫痫,尽早采用生酮饮食治疗可能有助于癫痫控制。

Objective To investigate the efficacy and safety of ketogenic diet(KD)therapy in the epilepsy of infancy with migrating focal seizures(EIMFS)associated with TBC1D24 gene mutation.Methods Clinical data of two children with TBC1D24 gene-related EIMFS were collected retrospectively,who were admitted to Department of Pediatrics,Fujian Medical University Union Hospital from 2019 to 2020.Their clinical characteristics and the efficacy and safety of KD therapy were analyzed,and literature review was conducted.Results Seizures were onset before six months old in the two children with TBC1D24 gene-related EIMFS.Multifocal myoclonic seizures were manifested and happened frequently,lasting for more than 30 minutes sometimes.Developmental retardation was obvious in the two children.A small amount of focal sharp,spike,sharp-slow complex,and spike-slow complex waves were showed in the interictal electroencephalography(EEG).TBC1D24 gene mutations were found in the two children,one with a compound heterozygous mutation(c.1025C>T,p.S342L;c.229_c.240delATCGTGGGCAAG,p.I77_K80del),and the other with a homozygous mutation[c.119G>A,p.R40H(Arg40His)].Both of those were potentially pathogenic.A variety of anti-epileptic drugs showed poor outcome for the two children.The epilepsy was drug-refractory one.After four to 17 months of KD therapy,the epilepsy in the two children was controlled effectively.There was not obvious adverse reactions.Among six children with TBC1D24 gene-related EIMFS in the literature review,four cases were effective or partially effective for KD therapy,one was discontinued due to insufficient ketogenic ratio,and one was discontinued without effect.There were no obvious adverse reactions in the six children.Conclusions TBC1D24 gene-related EIMFS is mostly drug-refractory epilepsy.Early KD therapy may help to control seizures.