ABSTRACT
Congenital hyperinsulinemic hypoglycemia(CHH)is a group of rare heterogeneous diseases with hypoglycemia as the main clinical manifestation caused by insulin imbalance and excessive secretion.It is the most common cause of persistent hypoglycemia in infants and children.Related gene mutations were detected in about 40% of patients, among which inactivating mutations in ABCC8 or KCNJ11 genes are the most common.Delay in diagnosis and improper treatment can cause permanent brain damage in infants and children with CHH.Therefore, early identification and correct diagnosis and treatment are important and essential to prevent brain damage in infants and children with CHH.This article reviews the molecular pathogenesis of CHH caused by K ATP gene inactivation mutations, the impact of ABCC8 or KCNJ11 gene mutations on the pathological types of pancreas, the severity of hypoglycemia and the choice of clinical treatment options in children with CHH, as well as the latest progress in clinical diagnosis and treatment of CHH, in order to improve clinicians′ awareness of CHH.
ABSTRACT
Objective To analyze the clinical characteristics and gene mutations of 56 patients with congenital hyperinsulinism(CHI)and to provide a theoretical basis for clinical diagnosis and treatment of CHI.Methods Fifty-six children who were diagnosed as CHI between February 2002 and January 2016 in Beijing Children's Hospital Affiliated to Capital Medical University were selected as research subjects.A retrospective study was done about the clinical data and the treatment procedures of the 56 patients,such as perinatal conditions,clinical manifestations,laboratory data,treatments,prognosis and so on.Polymerase chain reaction(PCR)-DNA technology or next-generation sequencing technology was used to analyze the CHI relevant genes of the 56 patients.Results Thirty of the 56 patients carried CHI gene mutation.(1)Twenty-three of 56 patients(41.0％)carried ABCC8/KCNJ11 gene mutations:4 of 23 patients carried complex heterozygous mutation,1 of 23 patients carried both ABCC8 and KCNJ11 gene mutation,1 of 23 patients carried maternally inherited ABCC8 gene mutation,12 of 23 patients carried paternally inherited ABCC8 gene mutation,1 of 23 patients carried paternally inherited KCNJ11 gene mutation,3 of 23 patients carried de novo ABCC8 gene mutation,1 of 23 patients had unknown genetic way,19 of 23 patients were treated with Diazoxide,2 of 19 patients were responsive to Diazoxide,7 of 19 patients were unresponsive to Diazoxide and 10 of 19 patients were uncertain to Diazoxide.(2)Five of 56 patients(8.9％)carried GLUD1 gene mutation,4 of 5 patients were treated with Diazoxide and they were all responsive to Diazoxide.(3)One of 56 patients(1.7％)carried de novo GCK gene mutation,responsive to Diazoxide treatment.(4)One of 56 patients(1.7％)carried maternally inherited SLC16A1 gene mutation,responsive to Diazo-xide treatment.Conclusions The ABCC8 gene and GLUD1 gene mutation are the main causative genes of CHI.The GCK gene and SLC16A1 gene mutation are in the minority.Most ABCC8 gene and KCNJ11 gene mutation are unresponsive to Diazoxide treatment.
ABSTRACT
Two patients with neonatal diabetes tested as V59A and V59M mutations were chosen for the study. Clinical data were analyzed retrospectively. The results showed that the patient with V59A mutation was characteristic of spasm and hyperglycemia at the age of three month, and treated with insulin for a long time as unresponsive to the glibenclamide at the beginning. Myasthenia and delay of development were observed during the follow-up. At the age of two years, glibenclamide was tried for the second time with a high dose and fairly-controlled glucose level. The patient with V59M mutation was diagnosed with diarrhea, hyperglycemia, and ketosis at the age of two month, and was responsive to glibenclamide at a relatively low dose with well-controlled glucose level. These results suggest that KCNJ11 V59M mutation would show some milder clinical manifestations and better glibenclamide efficacy as compared with V59A mutation.
ABSTRACT
Fourteen neonatal diabetes mellitus(NDM)patients were recruited. 9 patients were treated with glyburide and the other 5 with insulin. ABCC8, KCNJ11, and INS genes were sequenced in 6 of them. Gene mutations were found in 2, 1, and 1 cases in these genes, respectively. One case with 6q24 hypomethylation and another without known mutation were also found. 8 out of 9 patients treated with glyburide reached euglycemia(88.9%). The other 5 patients with insulin therapy either died or lost contact. The results suggest that glyburide therapy is effective in neonatal diabetes mellitus, while insulin therapy may contribute to poor compliance.
ABSTRACT
Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia in infancy. While most of the cases are sporadic more than 100 mutations have been reported in the familial type. The authors report a case of familial hyperinsulinemic hypoglycemia with homozygous T294M mutation of the KCNJ11 gene, which responded to diazoxide therapy.
Subject(s)
Antihypertensive Agents/therapeutic use , Congenital Hyperinsulinism/drug therapy , Congenital Hyperinsulinism/genetics , Diazoxide/therapeutic use , Female , Homozygote , Humans , India , Infant, Newborn , Mutation , Potassium Channels, Inwardly Rectifying/geneticsABSTRACT
KCNJ11 gene mutation was searched in 3 families with neonatal diabetes. A KCNJ11 175 G>A (V59M) mutation was found in one child, while no KCNJ11 gene mutation was found in his parents. No mutation was found in the other two families. The result indicated that KCNJ11 gene mutation might lead to the onset of neonatal diabetes mellitus in Chinese.