生酮饮食对基因变异相关癫痫疗效分析

doi:10.12372/jcp.2022.21e1415

摘要/Abstract

摘要：

目的分析生酮饮食治疗基因变异相关癫痫的临床疗效。方法回顾性分析2017年4月至2021年3月无锡市儿童医院诊治的10例基因变异相关癫痫患儿的临床特征、生酮饮食疗效及预后。结果 10例患儿中男4例、女6例。起病年龄为3天~16个月，生酮饮食治疗年龄为2月~12岁。所有患儿出生史正常，血液生化、头颅磁共振成像、血尿代谢筛查等均未见异常。5例患儿为SCN1A基因变异，2例为SLC2A1基因变异，另3例分别为SCN2A、KIF1A、PIGA基因变异。生酮饮食后随访6个月至4年5个月，4例患儿无发作，其中2例为SLC2A1基因变异，2例为SCN2A及PIGA基因变异。3例SCN1A基因变异的患儿发作减少≥50%，另2例SCN1A基因变异患儿发作减少<50%，1例患儿添加吡仑帕奈治疗后发作明显减少。KIF1A基因变异的患儿生酮饮食后发作无明显改善。结论生酮饮食对部分SLC2A1、SCN2A、PIGA、SCN1A基因变异的患儿有效。鉴定致病基因有助于预测生酮饮食的疗效。

关键词: 生酮饮食, 癫痫, 基因变异

Abstract:

Objective To analyze the clinical efficacy of ketogenic diet in the treatment of epilepsy with genetic etiology. Methods The clinical characteristics, ketogenic diet efficacy and prognosis of 10 epilepsy patients with genetic etiology treated in Wuxi Children's Hospital from April 2017 to March 2021 were retrospectively analyzed. Results here were 4 boys and 6 girls. The age of onset was 3 days to 16 months, and the age of ketogenic diet treatment ranged from 2 months to 12 years. The birth history was normal in each patient, and there was no abnormality in blood biochemistry, cranial MRI and hematuria genetic metabolism screening. SCN1A gene variation was found in 5 cases, and SLC2A1 gene variation was found in 2 cases. The other 3 cases had SCN2A, KIF1A and PIGA gene variation, respectively. During the follow-up period of 6 months to 4 years and 5 months after ketogenic diet, 4 cases had seizure free, including 2 cases of SLC2A1 variation and 2 cases of SCN2A and PIGA variation. Three patients with SCN1A variation had seizure reduction of more than 50%, and the other two patients with SCN1A variation had seizure reduction of less than 50%. The seizures of one child were significantly reduced after the addition of perampanel. The children with KIF1A gene variation had no significant improvement in seizures after ketogenic diet. Conclusions Ketogenic diet has a significant effect on some patients with refractory epilepsy, especially those with SLC2A1, SCN2A, PIGA and SCN1A variation. Identification of pathogenic genes is helpful to predict the efficacy of ketogenic diet.

Key words: ketogenic diet, epilepsy, gene variation

胡笑月, 井淼, 王艳萍, 华颖. 生酮饮食对基因变异相关癫痫疗效分析[J]. 临床儿科杂志, 2022, 40(12): 934-938.

HU Xiaoyue, JING Miao, WANG Yanping, HUA Ying. Effect of ketogenic diet on epilepsy with genetic etiology[J]. Journal of Clinical Pediatrics, 2022, 40(12): 934-938.

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序号	性别	起病年龄	生酮年龄	基因	变异	ASM	发作频率	发作类型
1	男	6月	13月	KIF1A	c.296C>T	VPA、TPM	每日数次	局灶性发作、痉挛发作、肌阵挛
2	女	16月	4.8岁	SLC2A1	c.476T>C	OXC、LEV	数月1次	局灶性发作、癫痫持续状态
3	女	2月	5月	SLC2A1	c.164_165 delinsTTCA	LEV、OXC	每日数次	局灶性发作
4	女	6月	10岁	SCN1A	c.5606T>C	VPA、LEV	2次/周	全身强直阵挛发作、局灶性发作、不典型失神
5	男	5月	4岁	SCN1A	c.580G>A	VPA、LEV、TPM、CZP	每周数次	全身强直阵挛发作、局灶性发作
6	女	5月	10月	SCN1A	c.3705+2T>C	VPA、LEV、TPM	每日数次	不典型失神，肌阵挛，癫痫持续状态
7	女	4月	12岁	SCN1A	c.135delC	VPA、TPM、CZP	每日数次~ 每3~5天1次	全身强直阵挛发作、局灶性发作
8	男	6月	18月	SCN1A	c.3733C>T （LOF）	LEV、VPA	1~2次/周	全身强直阵挛发作、局灶性发作、肌阵挛、癫痫持续状态
9	女	3天	2月	SCN2A	c.468G>C	VPA、TPM、OXC	每天数十次	局灶性游走性、全身强直阵挛发作
10	男	5月	18月	PIGA	c.241C>T	VPA、LEV、TPM	每日数次	局灶性发作、肌阵挛、全身强直阵挛发作、癫痫持续状态

序号	1个月内起效	治疗3个月	治疗6个月	治疗12个月	生酮时间	发育改善	不良反应
1	无	发作减少<50％	发作减少<50％	发作减少<50％	1年	否	腹泻
2	-	无发作	无发作	无发作	>1年	是	无
3	是，1周	无发作	无发作	无发作	>1年	是	低钙血症
4	否	发作减少≥50%	发作减少≥50%	发作减少≥50%	>1年	否	腹泻、纳差
5	否	发作减少≥50%	发作减少<50%	发作减少<50%	1年	否	无
6	是	发作减少≥50%	发作减少≥50%	发作减少≥50%	>1年	是	腹泻
7	是	无发作	无发作	发作减少≥50%	>1年	是	肾结晶
8	否	发作减少<50%	发作减少<50%	发作减少<50%	1年	否	便秘
9	是，1周	无发作	无发作	-	6月	是	无
10	否	发作减少≥50%	无发作	-	9月	是	纳差