摘要
目的分析ATP敏感性钾通道型先天性高胰岛素血症(KATP-HI)患儿的临床特征及遗传学特征。方法选取2002年2月至2018年12月间首都医科大学附属北京儿童医院收治的45例经遗传学确诊为KATP-HI的患儿及其家系为研究对象, 对患儿的临床特征、诊疗过程、致病基因突变情况和后期随访等资料进行回顾性分析。应用二代测序技术对KATP-HI相关致病基因ABCC8和KCNJ11进行测序分析。结果 45例KATP-HI患儿中, 新生儿期发病34例(75.6%), 21例(46.7%)首发症状为抽搐。39例应用二氮嗪治疗, 其中12例(30.8%)有效, 16例(41.0%)无效, 11例疗效不明确。对二氮嗪治疗疗效不确定或无效的患者中18例进一步应用奥曲肽治疗, 其中13例(72.2%)有效, 3例无效, 2例疗效不明确。10例因药物治疗无效或18氟-左旋多巴正电子发射计算机断层扫描(18F-DOPA PET)明确为局灶型病变患儿行外科手术治疗, 其中8例行胰腺部分切除术, 术后血糖均恢复正常;2例行次全胰腺切除术治疗, 术后均继发糖尿病。45例KATP-HI患儿中1例同时携带ABCC8和KCNJ11突变;10例携带ABCC8复合杂合突变;34例携带ABCC8或KCNJ11单基因突变, 其中父系遗传的KATP-HI患儿21例, 母系遗传的KATP-HI患儿3例, 新生突变的KATP-HI患儿6例。结论二氮嗪治疗对多数KATP-HI患儿无效, 而奥曲肽治疗有效率更高。局灶型病变的患儿行胰腺部分切除术治疗具有较高的治愈率, 次全胰腺切除术后有继发糖尿病的风险, 故术前明确患儿的胰腺组织学类型极为重要。ABCC8和KCNJ11基因突变是KATP-HI的主要致病基因, 携带ABCC8或KCNJ11单个基因突变的KATP-HI患者中, 以父系遗传者占多数。部分KATP-HI患儿低血糖症状可自行缓解。
Objective To analyze clinical characteristics and genetic characteristics of children with ATP sensitive potassium passage(KATP-HI).Methods Forty-five children with genetically confirmed KATP-HI and their families admitted to Beijing Children′s Hospital of Capital Medical University between February 2002 and December 2018 were selected as the study subjects.A detailed retrospective analysis of the patient's clinical characteristics,diagnosis and treatment process,disease-causing gene carrying status and later follow-up data was performed.ABCC8/KCNJ11 gene was sequenced by second-generation sequencing technology.Results Among 45 children with KATP-HI,34 cases(75.6%)were neonatal onset,the first symptoms of 21 cases(46.7%)were convulsions.39 cases had been treated with diazoxide,including 12 cases(30.8%)with good efficacy,16 cases(41%)with poor efficacy and 11 cases with uncertain efficacy.Octreotide was further applied in 18 patients with uncertain or ineffective efficacy after diazoxide treatment,and 13 cases(72.2%)were effective,3 cases were ineffective,and 2 cases were uncertain.10 CHI patients who were ineffective to drug treatment or had clearly focal lesions confirmed by 18F-dopa positron emission by computed tomography(18F-DOPA PET)scans had undergone surgical treatment,8 of which underwent partial pancreatectomy and blood glucose returned to normal after the operation;the other 2 cases underwent subtotal pancreatectomy and both had secondary diabetes after operation.Among 45 children with KATP-HI,1 case carried both ABCC8 and KCNJ11 mutations,10 cases carried ABCC8 compound heterozygous mutations,and the remaining 34 cases carried ABCC8/KCNJ11 single genetic mutation.Among them,21 cases had paternal inheritance,and 3 cases had maternal inheritance,6 cases were identified with de novo mutations.Conclusions Diazoxide treatment was ineffective for most KATP-HI children,but octreotide had a higher effective rate.Partial pancreatectomy for focal type patients had a higher cure rate,and there was a risk of sec
作者
惠培培
徐子迪
张琳
曾俏
刘敏
闫洁
吴玉筠
桑艳梅
朱逞
倪桂臣
李荣敏
王杰英
Hui Peipei;Xu Zidi;Zhang Lin;Zeng Qiao;Liu Min;Yan Jie;Wu Yuyun;Sang Yanmei;Zhu Cheng;Ni Guichen;Li Rongmin;Wang Jieying(Department of Pediatrics,Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,China;National Children′s Medical Center,Endocrine Genetic Metabolism Center,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Department of Endocrinology,Baoding Hospital,Beijing Children′s Hospital,Baoding Children′s Hospital,Key Laboratory of Children′s Respiratory and Digestive Disease Research,Baoding 071000,China)
出处
《中华胰腺病杂志》
CAS
2022年第1期48-54,共7页
Chinese Journal of Pancreatology
基金
首都临床特色应用研究资助项目(Z141107002514142)
保定市科技计划自筹经费项目(1951ZF076)。
关键词
高胰岛素血症
遗传性疾病
先天性
钾通道
点突变
二氮嗪
Hyperinsulinism
Genetic diseases,inborn
Potassium channels
Point mutation
Diazoxide
