Sirolimus in infants with congenital hyperinsulinism (CHI) - a single-centre experience

Abstract

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in neonates and infants. Medical treatment includes the use of high concentrations of glucose and combinations of diazoxide, octreotide and glucagon. We report our experience of using sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in the treatment of CHI in seven newborns who are poorly responding to standard medical therapy. Majority (87%) of infants achieved euglycaemia using a combination of oral feeding and the addition of sirolimus to standard medical treatment. One infant who failed to achieve euglycaemia even after surgery managed successfully with sirolimus. Diagnosis was confirmed by genetics evaluation; in three infants, novel mutations were detected. Outcome and long-term follow-up of all cases are described.Conclusion: Sirolimus can be considered in treatment of CHI refractory to standard medical treatment or in cases unresponsive to surgical treatment. What is Known: • Congenital hyperinsulinism (CHI) or persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) associated with mutations such as the ABBC8 or KCNJ gene known to cause hypoglycaemia refractory to standard medical treatment such as diazoxide and octreotide and may need subtotal pancreatectomy (STP). • Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, was recently reported to be useful for refractory CHI cases with variable efficacy. What is New: • Our case series describes efficacy and safety of sirolimus in seven genetically proven refractory CHI cases with mainly neonatal presentation. All patients' follow-ups are described. • Out of seven infants, six infants responded well to sirolimus, and among these one infant who failed to respond to surgery (STP) also successfully managed with sirolimus. • It highlights the right patient selection and right dose to successfully manage these cases without much adverse effects.

Keywords: Hyperinsulinism; Neonate; Novel ABCC8 mutation; Refractory hypoglycaemia; Sirolimus.