先天性高胰岛素血症4例临床诊治和致病基因分析
Clinical diagnosis,treatment,and genetic analysis in 4 cases of congenital hyperinsulinemia
王晓静 1许平 2石然然 3于永慧3
作者信息
- 1. 山东第一医科大学附属省立医院新生儿科,济南 250000;山东第一医科大学附属聊城医院新生儿重症医学科,聊城 252000
- 2. 山东第一医科大学附属聊城医院新生儿重症医学科,聊城 252000
- 3. 山东第一医科大学附属省立医院新生儿科,济南 250000
- 折叠
摘要
目的 探讨先天性高胰岛素血症(congenital hyperinsulinism,CHI)新生儿的临床诊治和基因变异情况.方法 选择2018年9月至2022年4月山东第一医科大学附属省立医院收治的CHI患儿的临床资料进行回顾性分析.结果 共纳入4例CHI患儿,足月儿3例,均为巨大儿,早产儿1例.母亲患妊娠期糖尿病及低血糖家族史各1例.4例均以反应差为主要表现,3例有嗜睡,1例伴肌张力低,1例病程中出现抽搐、拒乳,1例颅脑MRI提示顶枕叶皮质异常信号.基因测序1例为KCNJ11基因c.799C＞G纯合变异,3例ABCC8基因杂合变异,分别为c.4477C＞T和c.3540C＞G、c.683G＞A、c.4536C＞A,均为致病性变异.其中 KCNJ11 基因中 c.799C＞G和 ABCC8 的 c.3540C＞G、c.4536C＞A 变异位点为未报道过的新发变异.3例应用二氮嗪治疗,1例有效为KCNJ11基因变异,2例无效均为ABCC8基因变异.1例存在低血糖脑损伤的患儿家长放弃治疗;3例好转出院,随访至1岁,2例停药后血糖稳定,1例仍需间断口服葡萄糖维持血糖.结论 CHI易导致低血糖脑损伤,临床上对巨大儿、有糖尿病及低血糖家族史的患儿生后应早期监测血糖,尽早识别CHI并积极治疗,基因变异不同对药物的治疗反应不同.
Abstract
Objective To investigate the clinical diagnosis,treatment,and genetic variations of neonates with congenital hyperinsulinism(CHI).Methods The clinical data of CHI newborns admitted to the Provincial Hospital Affiliated to Shandong First Medical University from September 2018 to April 2022 were retrospectively analyzed.Results Four cases of CHI were included,three of whom were full-term infants and all were macrosomic,while one was a premature infant.One infant was born to a mother with gestational diabetes mellitus,and 1 had a family history of hypoglycemia.All the 4 patients presented with weak response,3 with drowsiness,1 with hypotonia and 1 with convulsions.Cranial MRI indicated abnormal signals in the occipital lobe cortex in 1 case.Gene sequencing revealed homozygous variation c.799C＞G in KCNJ11 gene for 1 case,and heterozygous variations c.4477C＞T,c.3540C＞G,c.683G＞A and c.4536C＞A in ABCC8 gene for 3 cases respectively and all these variations were identified as pathogenic mutations.Notably,the c.799C＞G variant in KCNJ11 gene as well as the c.3540C＞G and c.4536C＞A variants in ABCC8 gene were reported for the first time.Among infants with ABCC8 gene variations,two showed no response to diazoxide treatment while one patient with KCNJ11 gene variation responded effectively.The parents of the patient with hypoglycemic brain injury gave up treatment.Three other cases were discharged from hospital after improvement and followed up to 1 year old.2 patients had stable blood glucose after ceasing medication,and 1 patient still required intermittent oral glucose to maintain normal blood glucose level.Conclusions CHI can lead to hypoglycemic brain injury.Clinically,infants large for gestational age or with a family history of diabetes and hypoglycemia should be monitored for blood glucose early after birth,to identify CHI as early as possible and actively treat it.Different gene variants have different therapeutic responses.
关键词
先天性高胰岛素血症/低血糖/基因/KCNJ11/ABCC8Key words
Congenitalhyperinsulinism/Hypoglycemia/Gene/KCNJ11/ABCC8引用本文复制引用
基金项目
山东省重点研发计划(2018GSF118173)
出版年
2024
NETL
NSTL
万方数据