FBP1基因突变致果糖1,6二磷酸酶缺乏的癫持续状态1例并文献复习

目的：报告1例经基因诊断的果糖1,6二磷酸酶缺乏症致反复癫持续状态发作患儿,提高对该病的认识,为癫持续状态的病因评估提供参考。方法：总结1例反复癫持续状态发作并经基因检测诊断为果糖1,6二磷酸酶缺乏症患儿的临床资料及诊疗经过。行文献复习,总结FBP1基因突变致果糖1,6二磷酸酶缺乏症患儿的临床表现及基因突变特点。 结果：男,2岁5月龄,因“1年内惊厥发作4次”就诊。首次惊厥发作于16月龄,4次发作均表现为全面性强直阵挛,呈持续状态,前2次发作伴发热,外院先后诊断为“病毒性脑炎”、“热性惊厥”、“癫”,予左乙拉西坦口服治疗。追问病史,其中2次发作伴有低血糖和高乳酸血症。全外显子检测发现患儿FBP1基因c.704delC和c.959dupG复合杂合突变,家系验证发现突变分别来自父亲（c.704delC）和母亲（c.959dupG）。基因诊断后予患儿营养指导,避免长时间禁食或摄入富含果糖的食物并停用抗癫药物,随访2年未再发作。患儿母亲第2胎产前基因检测显示,胎儿携带母亲来源的突变,无父亲来源的突变,为单杂合突变携带者。文献复习发现68.5%病例起病于新生儿及婴儿期,主要诱因为感染和食物摄入不足,主要的临床表现为意识障碍、惊厥、消化道症状伴代谢性酸中毒、低血糖和高乳酸血症。结论：癫持续状态的病因复杂,应重视发作期代谢指标监测,早期明确病因并针对性治疗有利于改善预后,基因检测有助于明确遗传病因并指导优生优育。

Status epilepticus due to fructose-1,6-bisphosphatase deficiency caused by FBP1 gene mutation: case report and review of literature

Objective：To report a case of fructose-1,6-bisphosphatase deficiency diagnosed by genetic sequencing, and to improve the cognition of this rare disease and etiological diagnosis of status epilepticus (SE). Methods：Clinical data of the patient with FBP1 gene mutation from Children's Hospital of Fudan University were collected. The related literature was searched from Wanfang Data Service Platform, China National Knowledge Infrastructure and PubMed (up to October 2017) by using search terms "FBP1" and "Fructose-1,6-bisphosphatase deficiency". Results：A male patient with fructose bisphosphatase-1(FBP1) gene mutations who presented with SE and was misdiagnosed and treated with levetiracetam was reported. Genetic analysis of the family members revealed that the proband had compound heterozygous mutations of c.704delC and c.959dupG, which were inherited from his carrier parents, respectively. After genetic diagnosis, the patient was instructed to avoid prolonged fasting and to have fructose-free foods and finally withdrew from antiepileptic drugs. No seizures occurred during two years of follow-up. Sequencing of the amniotic fluid cells of the second child showed that the fetus only carried one heterozygous mutation which was inherited from the mother. According to the literature, 68.5% of cases had an onset in newborns or infancy, and the main causes were infection and inadequate intake. Main clinical manifestations were disturbance of consciousness, convulsions, gastrointestinal symptoms with hypoglycemia and lactic acidosis. Conclusion：For children manifested as recurrent SE with hypoglycemia, metabolic disorders should be considered. Correct diagnosis in early episodes is very important to improve the prognosis. Genetic counseling may be helpful to the family.