ABCC8基因复合杂合突变致儿童KATP-HI 9例临床分析  

Clinical analysis of 9 children with KATP-HI caused by compound heterozygous mutation of ABCC8 gene

作　　者：曾俏 徐子迪[1] 张琳 吴玉筠[1] 刘敏[1] 闫洁[1] 桑艳梅[1] 朱逞[1] 倪桂臣[1] Zeng Qiao;Xu Zidi;Zhang Lin;Wu Yuyun;Liu Min;Yan Jie;Sang Yanmei;Zhu Cheng;Ni Guichen(Department of Endocrinology,Genetics and Metabolism,Beijing Children's Hospital,Capital Medical University/National Center for Children's Health,Beijing 100045,China;不详)

机构地区：[1]国家儿童医学中心/首都医科大学附属北京儿童医院内分泌遗传代谢科,100045 [2]成都市第二人民医院儿科,610017

出　　处：《疑难病杂志》2022年第6期624-627,637,共5页Chinese Journal of Difficult and Complicated Cases

基　　金：北京市自然科学基金资助项目(7212034)。

摘　　要：目的分析ABCC8基因复合杂合突变导致的儿童ATP敏感钾通道型先天性高胰岛素血症(KATP-HI)的临床特征及遗传学特征。方法收集2012年5月—2017年8月北京儿童医院内分泌遗传代谢科诊治携带ABCC8基因复合杂合突变的9例KATP-HI患儿为研究对象,回顾性分析其临床特征、致病基因携带情况、治疗与随访资料。结果9例患儿均携带ABCC8基因复合杂合突变,突变类型包括错义突变(12/18,66.7%)、无义突变(4/18,22.2%)和移码突变(2/18,11.1%)。其中,新生儿期起病6例(66.7%),生后1~6个月内起病2例(22.2%),生后6个月后起病1例(11.1%)。正常出生体质量儿2例(22.2%),巨大儿6例(66.7%),低出生体质量儿1例(11.1%)。9例患儿中,8例曾应用二氮嗪试验性治疗,其中无效5例(62.5%),有效3例(37.5%)。4例曾应用奥曲肽治疗,均有效。经长期随访,3例患儿自行缓解,2例患儿需长期应用奥曲肽治疗,3例患儿通过少量多餐饮食控制血糖,当空腹时间延长时,偶有低血糖发作,失访1例。结论中国KATP-HI儿童的ABCC8基因复合杂合突变类型多样,以错义突变为主。携带ABCC8基因复合杂合突变的患儿多为巨大儿,多于新生儿期发病。该型患儿多对二氮嗪治疗不敏感,部分对奥曲肽治疗有效。随着病程进展,部分患儿可获得自行缓解。Objective To analyze the clinical and genetic features of children with ATP-sensitive potassium channel congenital hyperinsulinemia(KATP-HI)caused by compound heterozygous mutations in the ABCC8 gene.Methods Nine children with KATP-HI who were diagnosed and treated by the Department of Endocrinology,Genetics and Metabolism of Beijing Children's Hospital from May 2012 to August 2017 with compound heterozygous mutation of ABCC8 gene were collected as research objects.The clinical features,pathogenic gene carriers,treatment and follow-up data were retrospectively analyzed.Results All 9 children carried compound heterozygous mutation of ABCC8 gene,and the mutation types included missense mutation(12/18,66.7%),nonsense mutation(4/18,22.2%)and frameshift mutation(2/18,11.1%).Among them,6 cases(66.7%)had onset in the neonatal period,2 cases(22.2%)within 1 to 6 months after birth,and 1 case(11.1%)after 6 months after birth.There were 2 infants with normal birth weight(22.2%),6 infants with macrosomia(66.7%),and 1 infant with low birth weight(11.1%).Among the 9 children,8 patients had been treated with diazoxide experimental treatment,of which 5 patients(62.5%)were ineffective and 3 patients(37.5%)were effective.4 cases had been treated with octreotide,all were effective.After long-term follow-up,3 patients remitted spontaneously,2 patients required long-term treatment with octreotide,3 patients controlled their blood sugar through small and frequent meals,and occasionally hypoglycemia occurred when the fasting time was prolonged,and 1 patient was lost to follow-up.Conclusion There are various types of compound heterozygous mutations in the ABCC8 gene in Chinese KATP-HI children,and missense mutations are the main ones.Children with compound heterozygous mutation of ABCC8 gene are mostly macrosomia,more than neonatal onset.Most of the children with this type are insensitive to diazoxide treatment,and some are effective to octreotide treatment.With the progression of the disease,some children can get spontaneous remission.

关 键 词：先天性高胰岛素血症 ATP敏感性钾通道 复合杂合突变 ABCC8基因 二氮嗪 

分 类 号：R587.3[医药卫生—内分泌]