低磷酸酯酶症致儿童癫痫的基因型及临床表型分析并文献复习

doi:10.3760/cma.j.cn441417-20250713-21012

摘要/Abstract

摘要： 患儿男，发病年龄为3岁9个月，临床以反复癫痫发作为核心症状，血碱性磷酸酶（ALP）下降，头颅核磁检查无结构性异常及钙化灶，脑电图背景活动正常，清醒期出现以双侧额区为著的前头部棘慢波阵发，延续至睡眠期，睡眠期呈电持续状态。二代测序显示存在肝-骨-肾碱性磷酸酶（alkaline phosphatase liver/bone/kidney，ALPL）基因变异，为杂合突变，突变位点c.100C>T，该位点变异后引起蛋白翻译终止，属于常染色体显性遗传。该患儿确诊儿童型ALPL基因相关低磷酸酯酶症（hypophosphatasia，HPP），给予维生素B6联合左乙拉西坦治疗，临床发作可控制，脑电图仍持续异常放电，目前长期规律随访中。以“ALPL基因”“低磷酸酯酶症”“癫痫”为关键词，对中国知网、万方数据库知识服务平台及中华医学期刊全文数据库2015年1月至2025年3月收录的论文进行检索，归纳总结中国儿童HPP的基因型特点。

关键词: 儿童, 低磷酸酯酶症, 血碱性磷酸酶, 癫痫, ALPL基因

Abstract: The boy, whose age of onset was 3 years and 9 months old, presented with recurrent seizures as the primary clinical manifestation, along with decreased blood alkaline phosphatase (ALP). Brain MRI revealed no structural abnormalities or calcifications. The electroencephalogram (EEG) showed normal background activity with slow wave bursts in the anterior head region, predominantly in the bilateral frontal areas during wakefulness and persisting into the sleep period, accompanied by electrical persistence during sleep. Second-generation sequencing identified a heterozygous mutation in the alkaline phosphatase liver/bone/kidney (ALPL) gene at the c.100C>T site, resulting in premature protein translation termination and following an autosomal dominant inheritance pattern. The boy was diagnosed with childhood hypophosphatasia (HPP) related to the ALPL gene mutation and was treated with a combination of vitamin B6 and levetiracetam, resulting in manageable clinical seizures but persistent abnormal EEG discharges. Long-term regular follow-up was currently ongoing. A literature search using keywords "ALPL gene" "hypophosphatasia" "epilepsy" was conducted in the CNKI, Wanfang Database Knowledge Service Platform, and China Medical Journal Full-text Database from January 2015 to March 2025 to summarize the genotypic characteristics of HPP in Chinese pediatric patients.

Key words: Child, Hypophosphatasia, Alkaline phosphatase, Epilepsy, ALPL gene

何运元谢冰张军利蔡书芳. 低磷酸酯酶症致儿童癫痫的基因型及临床表型分析并文献复习[J]. 国际医药卫生导报, 2025, 31(21): 3581-3586.

He Yunyuan, Xie Bing, Zhang Junli, Cai Shufang. Genotypic and clinical phenotypic analysis of hypophosphatasia-induced epilepsy in children and literature review[J]. International Medicine and Health Guidance News, 2025, 31(21): 3581-3586.

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