A CASE REPORT ON CONGENITAL HYPERINSULINISM DUE TO ABCC8 GENE MUTATION

Abstract

INTRODUCTION
Congenital Hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants. It is a disorder caused by dysregulation of insulin secretion from pancreatic β-cells. There are 12 different gene mutations identified at this moment with ABCC8 and KCNJ11 genes mutation encode SUR 1 and KIR 6.2 subunit of the ATP-sensitive potassium channel (KATP) being the most common. Children with homozygous ABCC8 and KCNJ 11 mutations usually do not respond to diazoxide.

CASE
We report a female Indonesian infant with autosomal recessive CHI secondary to ABCC8 gene mutation. She was born term with birth weight of 4080 gram without history of maternal gestational diabetes. She developed symptomatic hypoglycemia at 10 hours of life with random blood glucose of 1.7 mmol/L. She needed a high glucose delivery rate up to 18 mg/kg/min and glucagon infusion to maintain normoglycemia. Critical blood sampling confirmed hyperinsulinism with an elevated serum insulin level of 18.1 U/ml at a random plasma glucose of 1.6 mmol/L. She had recurrent hypoglycemia despite an optimal dose of diazoxide. Subsequently, she was transferred to our center at the age of 2 months and started on subcutaneous octreotide injection four times daily; needing up to 35 mcg/ kg/day to maintain blood glucose levels above 4 mmol/L. Genetic testing revealed a homozygous mutation in the ABCC8 gene which is known to be associated with poor response to oral diazoxide. Recessive ABCC8 mutation is associated with diffuse form of CHI hence optimizing medical treatment will be the preferred option before deciding for near total pancreatectomy.

CONCLUSION
This case illustrates a severe neonatal hypoglycemia unresponsive to diazoxide, where genetic confirmation helps to prognosticate the outcome and to plan for treatment strategy. It is vital to make an early diagnosis of CHI and initiate appropriate management to prevent hypoglycemia related permanent neurological damage.