ABSTRACT
Objective:To explore the clinical features, treatment, prognosis and genetic mutation in neonatal congenital hyperinsulinemia(CHI).Methods:Neonates with CHI admitted to the neonatal intensive care unit of Hebei Provincial Children′s Hospital from February 2017 to August 2020 were selected, and their clinical characteristics, diagnosis and treatment, prognosis and genetic mutation were retrospectively analyzed.Results:A total of seven neonates were enrolled.The average gestational age was(38.1±1.5)weeks with two cases gestational age<37 weeks.The mean birth weight was(3 608±906)g with three cases birth weight>4 000 g. The common clinical manifestations included lethargy, poor feeding, cyanosis, seizures, and tremble.Non-specific manifestations were observed in two premature infants, whose blood glucose were found very low during the routine monitoring at 1 hour and 3 hours after birth respectively.Among the seven cases, six cases needed high glucose infusion rate(GIR)[>10 mg/(kg·min)] to maintain the serum glucose at the normal level from the beginning.Only one case needed lower GIR[3-5 mg/(kg·min)] on admission while gradually increased to 8 mg/(kg·min) maximumly during hospitalization.All seven neonates were treated with diazoxide orally, and two cases(2/7) were effective, including one case who discontinued the drug at six months after birth with normal blood glucose level.The remaining five neonates(5/7) were diazoxide resistant due to mutations in the ABCC8 gene encoding the K ATP+ -channel of the pancreatic beta cell and then treated with octreotide.Two cases(2/5) of them were effective to octreotide and the other three cases(3/5) were both diazoxide and octreotide resistant.One case died after withdrawal from the treatment and the other one lost follow-up.The other five cases were followed up until now.Normal neurological development were found in three cases.Two cases were found with epilepsy and moderate developmental delay in language and social competence ability during the follow up.Mutations in ABCC8 were the most common in seven cases, of which six cases were heterozygous mutation of ABCC8 and one case was heterozygous mutation of GLUDI. Conclusion:The clinical manifestations of CHI are non-specific.The blood glucose level of the high-risk neonates should be timely monitored.Neonates who needs lower GIR[<8 mg/(kg·min)] at the early stage can not be completely excluded CHI.Some CHI cases may self-resolved after several months.Molecular diagnosis can identify the pathogenic genes, which is important to achieve accurate diagnosis and treatment, and thus improve the prognosis of patients with CHI.
ABSTRACT
Congenital hyperinsulinemia (CHI) is a genetically and clinically heterogenous disorder. In addition to the standard care of management of the proband, genetic counseling regarding the risk of recurrence in the future siblings is an important part in the management of the disorder. The counseling needs identifcation of accurate etiology and is challenging due to the complexity of the molecular mechanisms of CHI. This case highlights the importance of molecular testing which not only helped in planning the management of the proband with CHI but also helped in providing genetic counseling for which the family had consulted the medical genetics department.