Endocrine Abstracts

Introduction: Congenital hyperinsulinism (CHI) is a rare disease, characterized by an unregulated insulin release, leading to hypoglycaemia. It is the most frequent cause of persistent and severe hypoglycaemia during the neonatal period and early childhood. Mutations in K_ATP < genes (ABCC8 and KCNJ11), together account for up to 70% of CHI. CHI can either be transient or persistent. Transient CHI tends to resolve spontaneously and is not generally associated with genetic mutations. We present two cases with: [1] transient CHI & [2] mild (and potentially transient) CHI, associated with heterozygous mutations in ABCC8 and KCNJ11 respectively.

Cases: 1. A term infant (birth weight: 3.2 kg), with no risk factors for hypoglycaemia, presented with seizures associated with a blood glucose (BG):0.5 mmol/l on day 2 of life. The investigations confirmed CHI, which was fully responsive to low dose of diazoxide (3 mg/kg/day). At 18 months, a 12 hour fast off diazoxide showed normoglycaemia with supressed insulin and appropriate increase in the ketone bodies indicating the resolution of CHI. The genetic testing showed a novel ABCC8 variant (c.2476C>A). The parental testing is underway.

2. A term infant (birth weight: 4.3 kg), with no risk factors for hypoglycaemia, presented on day 3 of life with seizures, associated with a BG:<0.2 mmol/l. Subsequent investigations confirmed CHI, which was completely responsive to diazoxide (5 mg/kg/day). Genetic testing identified a maternally-inherited KCNJ11 loss-of-function missense variant (p.Gly40Asp) of uncertain significance, as the mother appears clinically unaffected and did not have gestational diabetes. BG levels for the child are currently stable (>3.5 mmol/l) at 1 year of age at a diazoxide dose of 3 mg/kg/day. A controlled fast off diazoxide is awaited.

Discussion: Genetic testing is not normally indicated for transient CHI, but potentially should be considered if there are no associated risk factors. Although the clinical significance of K_ATP mutations is currently unclear in the above two patients, it may have implications for postnatal BG monitoring in subsequent pregnancies, particularly due to the risk of neonatal hypoglycaemia and neurodevelopmental sequelae. Due to the associated gene locus, they may also have a predisposition to develop diabetes in later life, implying the need for long-term monitoring.