FBP1突变致果糖-1,6-二磷酸酶缺乏症2例临床及基因研究

Clinical and genetic studies of two cases of fructose-1,6-bisphosphatase deficiency caused by FBP1 mutations

目的分析2例果糖-1,6-二磷酸酶缺乏症(FBP1D)患儿的临床及分子遗传学特点,为患儿的治疗、该家系的遗传咨询及产前诊断提供依据。方法对2017年12月至2018年1月郑州大学附属儿童医院康复中心收治的2例低血糖脑病患儿进行临床资料收集,并应用靶向捕获二代测序的方法进行分子遗传学分析。结果病例1.即先证者,男,7岁,主要表现为饥饿或摄入大量果糖后出现抽搐,多伴酮症酸中毒,临床诊断为低血糖脑病,疑似果糖代谢异常。病例2.先证者同胞弟弟,4岁,主要表现为晨起饥饿、多汗,进食水果后腹痛,曾饥饿后抽搐1次。二代测序结果显示两例患者在FBP1基因存在c.333+12delinsTC和c.490G>A复合杂合突变,父母均为正常表型的携带者。其中c.333+12delinsTC为未报道的新突变,c.490G>A为已报道致病突变,可基因确诊为果糖-1,6-二磷酸酶缺乏症。结论对于不明原因的低血糖、抽搐、代谢性酸中毒患儿,应考虑果糖-1,6-二磷酸酶缺乏症可能,及早进行分析遗传学分析,明确病因,有助于准确的指导治疗、改善患儿预后。

Objective To analyze the clinical and molecular genetic characteristics of 2 cases of fructose-1,6-bisphosphatase deficiency in the same family to provide evidence for the precise treatment,genetic counseling and prenatal diagnosis.Methods Clinical data were collected from 2 patients with hypoglycemia encephalopathy,and molecular genetic analysis was performed using targeted capture next-generation sequencing. Results The 2 patients were siblings,the male proband was 7 years old,mainly manifested with convulsions after hunger or ingestion of a large amount of fructose,accompanied by ketoacidosis;clinical diagnosis was hypoglycemia encephalopathy,and fructose metabolism abnormalities was suspected. The younger brother was 4 years old,mainly showing hunger and sweating in the morning,stomach ache after eating fruit,and convulsion episode once after hunger. Next-generation sequencing results showed that the siblings had c.333+12 delinsTC and c.490 G>A compound heterozygous mutations in the FBP1 gene,and their parents were carriers with normal phenotype.The c.333+12 delins TCis a novel mutation,c.490 G>A is a reported pathogenic mutation,and the two patients were diagnosed with fructose-1,6-bisphosphatase deficiency genetically. Conclusion For children with unexplained hypoglycemia,convulsions and metabolic acidosis,the fructose-1,6-bisphosphatase deficiency should be considered. Early genetic analysis is helpful to clarify the cause,make precise treatment and improve prognosis.