Sirolimus precipitating diabetes mellitus in a patient with congenital hyperinsulinaemic hypoglycaemia due to autosomal dominant ABCC8 mutation.

BACKGROUND: Sirolimus (mTOR inhibitor) is proven to be effective in children with congenital hyperinsulinism (CHI). Studies in animals suggest that sirolimus may have diabetogenic actions. However, its role in precipitating diabetes mellitus (DM) in children with CHI has not been reported.

CASE PRESENTATION: A 16-year-old female with CHI due to a dominant ABCC8 gene mutation was switched from diazoxide therapy to sirolimus, due to the hypertrichosis side effect of diazoxide. She developed facial cellulitis that was treated with clarithromycin and a month later, once the infection was resolved, she was found to have persistent hyperglycaemia, and was diagnosed with DM. She was unresponsive to oral sulfonylurea therapy and is currently managed with metformin. Her mother, who had the same ABCC8 mutation, developed DM at her 30s.

CONCLUSIONS: Patients with dominant ABCC8 gene mutations are prone to DM in adulthood, but Sirolimus therapy might increase the risk of developing diabetes at an early age, as this case illustrates.