吡哆醇依赖性癫痫的临床特点与基因特点分析

Clinical and genetic characteristics of pyridoxine-dependent epilepsy

目的分析4例吡哆醇依赖性癫痫(pyridoxine-dependent epilepsy,PDE)患儿的临床特征及分子生物学特征,为早期识别PDE提供临床依据。方法选取2016年1月至2019年6月于西安交通大学第二附属医院儿科神经组住院部治疗的4例PDE患儿的临床资料及血液生化、脑电图、头颅磁共振成像(MRI)等结果,抽取患儿及患儿父母的外周静脉血,从白细胞中提取基因组DNA,通过设计引物,使用PCR技术扩增5号染色体长臂上的致病基因乙醛脱氢酶7家庭成员A1(aldehyde dehydrogenase 7 family member A1,ALDH7A1)的外显子及外显子与内含子交界区,进一步测序明确是否有基因突变。结果①临床特点。发病时间:生后8 d至生后6个月。发作类型:1例以肌阵挛起病,后转为痉挛发作,1例为全面性发作,2例为部分性发作起病,后转为全面性发作;其中3例易出现癫痫持续状态,1例感染后发作明显加重。头颅MRI:3例未见异常,1例显示非特异性异常。脑电图特点:1例不典型高峰失律,3例为背景活动慢,发作间期放电以后头部为主。治疗特点:4例均为小剂量维生素B6口服即可控制发作,其中1例在很小剂量时发作就得到控制。②基因分析结果。4例患儿中均有ALDH7A1基因突变,其中3例是已知基因突变,1例为新发突变。结论PDE起病早,常于新生儿或婴儿期起病,易出现癫痫持续状态,感染时发作程度明显加重,发作类型、脑电图及头颅MRI均无特异性;对ALDH7A1基因分析有助于早期确诊;小剂量维生素B6口服即可控制发作,为临床应用提供参考。但由于病例数较少,需大样本病例进一步验证。

Objective To analyze the clinical features and gene mutation characteristics of four children with pyridoxine-dependent epilepsy(PDE)in order to provide evidence for early diagnosis of this rare disease.Methods The clinical data of four cases of PDE were collected from January 2016 to June 2019 in The Second Affiliated Hospital of Xi’an Jiaotong University.We collected data of the laboratory examination,electroencephalogram,and magnetic resonance imaging(MRI).Peripheral venous blood was collected from children and parents,genomic DNA was extracted from white blood cells,and primers were designed to amplify the aldehyde dehydrogenase 7 family member A1(ALDH7A1)on the long arm of chromosome 5 using PCR;exon and the junction of exon and intron were also amplified to determine whether there is a gene mutation.Results All the 4 cases had a full-term birth and no history of birth asphyxia.①Clinical features:onset time from 8 days after birth to 6 months after birth.Type of seizure:1 case with myoclonus onset,then converted to spasm;1 case for generalized seizures;2 cases for partial seizures,then converted to generalized seizures;3 cases were prone to epileptic seizures;1 case was significantly worse after infection;MRI:3 cases showed no abnormalities,1 case showed non-specific abnormalities;EEG:One case was fragmentary hypsarrhythmia,3 cases of multifocal epileptiform discharge;Treatment:a small dose of vitamin B6 could control the seizure,1 of them was controlled at a tiny dose,and 3 caseswere controlled by a small dose.②Genetic analysis results:There were 4 cases of ALDH7A1 gene mutation,of which 3 cases were known gene mutations and 1 case was new mutation.Conclusion PDE has an early onset,often in the neonatal or small infancy,is prone to epilepticus and has an increased severity after infection.There is no specificity in seizure type,EEG or MRI.The analysis of ALDH7A1 gene and vitamin B6 load test can help to confirm the diagnosis,small dose of Vitamin B6 can control the seizures so as to provide reference for the dose of vitamin B6.However,the number of cases is small,and a large sample size is still needed for verification.