ESPE Abstracts

Background: Hyperinsulinism represents a group of clinically, genetically and morphologically heterogeneous disorders characterised by β-cell dysfunction in glucose homeostasis leading to excessive insulin secretion with profound and recurrent hypoglycaemia. In most countries it occurs in approximately 1/25,000 to 1/50,000 births. Mutations in at least 14 genes have been reported to cause congenital hyperinsulinism. In nearly half of the cases, cause remains uncertain.

Clinical description: Two female siblings both born at term 3 years apart, both small for gestational age, antenatal history of assumed maternal gestational diabetes in both pregnancies, both presenting with decreased oral acceptance, lethargy, grunting, jitteriness and hypoglycaemia in the first 6 hours of age. Two male siblings born 4 years apart, both born at term after uneventful antenatal period, both presenting in the first 4 hours of age with similar clinical picture compared to the newborn females. Predisposing factors for hypoglycaemia (infection, IUGR, perinatal asphyxia, maternal diabetes) were ruled out.

Management: All newborns had recurrent episodes of hypoglycaemia and required a glucose infusion rate up to 13.5 mg/kg/min to maintain blood glucose levels. All babies required glucagon infusion and diazoxide to achieve normoglycaemia. The hypoglycaemia was confirmed to be related with hyperinsulinism. The female infants required Diazoxide for approximately 5 months, the male infants for 9 months. At present, the four children are normoglycaemic and achieving their milestones. However, the two brothers presented with ketotic hypoglycaemia with intercurrent illnesses.

Genetic Studies: Both females were confirmed to have congenital hyperinsulinism with a heterozygous missense mutation at c.3539T>A on INS receptor. The females’ mother, grandfather, maternal brothers, and grandfather’s brother had been diagnosed with Type 2 Diabetes Mellitus, despite their low BMI. They were all tested and proven to have the same mutation. Both males had genetic studies, but no genetic mutation/variant was identified.

Conclusion: We report 4 cases of hyperinsulinism in neonates with similarities on presentation and clinical progress, although not sharing a genetic cause. There are possible genetic changes yet to be identified. These cases highlight the importance of prompt diagnosis of persistent hypoglycaemia in neonates and prevention of complications such as neurodevelopmental deficits. Further monitoring will inform us of the clinical course through to adult life. Lifestyle modifications could play a key role in long-term management, due to possible risk of patients developing diabetes mellitus, but these are no different from the healthy life style advice given to the general population.