先天性高胰岛素血症致病基因的研究进展

Research progress in genetic mechanism of congenital hyperinsulinemia

先天性高胰岛素血症(CHI)是一种胰岛素分泌失调的遗传性疾病,是小儿持续性低血糖的重要原因。近年对其遗传机制的研究发现,参与调控胰腺β细胞胰岛素分泌的关键基因突变是导致CHI的原因,其中包括ABCC8、KCNJ11、KCNQ1、CACNA1D、SLC16A1、GLUD1、GCK、HADH、UCP2、HK1、PMM2、PGM1、HNF1A、HNF4A和FOXA2。这些基因突变导致三磷酸腺苷敏感型钾通道(KATP)改变、酶基因缺陷、转录因子基因缺陷,进而影响胰岛素的分泌,而这些遗传机制将会决定CHI的治疗方式。不同的基因突变,甚至相同基因的不同突变类型,均会影响CHI的治疗方式。二氮嗪作为CHI的一线用药,仅对于KATP通道完整或显性遗传的KATP突变引起的CHI患者有效。对于内科治疗无效者,可手术治疗,局灶型CHI患者手术切除病灶后可治愈,但弥漫型CHI术后效果较差,且并发症较多。

Congenital hyperinsulinemia(CHI)is a genetic disorder of insulin secretion disorder,constituting an important cause of persistent hypoglycemia in children.With the deeper discovery of the genetic mechanism of CHI in recent years,mutations of key genes involved in the regulation of pancreaticβ-cell insulin secretion have been found to be the cause of CHI including ABCC8,KCNJ11,KCNQ1,CACNA1 D,SLC16 A1,GLUD1,GCK,HADH,UCP2,HK1,PMM2,PGM1,HNF1 A,HNF4 A,and FOXA2.Mutations in these genes lead to changes in ATP-sensitive potassium channels(KATP),enzyme gene defects and transcription factor gene defects,which in turn affect insulin secretion,these genetic mechanisms would determine the treatment of CHI.Different gene mutations,or even different mutation types of the same gene,can affect the treatment modalities for CHI.Diazoxide,as a first-line drug for CHI,is only effective in patients with CHI caused by KATP mutations with intact or dominantly inherited KATP channels.For those who fail to respond to medical treatment,surgical treatment can be performed,and patients with focal CHI can be cured after surgical resection of the lesion,but diffuse CHI has poor postoperative results and more complications.