Background: Congenital hyperinsulinism (CHI) represent a group of clinically and genetically heterogonous disorder that characterized by unregulated insulin secretion by B-cells. It is the most common cause of hypoglycaemia in the neonatal period. Infants with diffuse CHI have homozygous or compound heterozygous mutation in the KATP channel and the majority are unresponsive to standard medical therapy and eventually they need near total pancreatectomy. Recent data showed the efficacy of MTOR inhibitor in adult patients with insulinoma and neonate with sever diffuse CHI and were managed with Sirolimus therapy avoiding pancreatectomy.
Objective and hypotheses: To test Sirolimus therapy response in three Saudi infants with sever CHI, confirmed mutation in KATP channel who failed medical therapy with Diazoxide and Octreotide treatment.
Method: Three Saudi infants who presented in the neonatal period with sever non ketotic hypoglycaemia, biochemically confirmed CHI, all of them were on high glucose infusion rate, require high dose Diazoxide (20 mg/kg per day) and Octreotide (45 μg/kg per day) therapy were subjected to Sirolimus therapy trial, two patients had Sirolimus trial preoperatively and one post near total pancreatectomy with a dose range from 1.2 to 4.5 mg daily.
Results: One case the genetic test confirmed mutation in exon 1 of KCNJ11 gene, the second case is the double cousin of case 1 and the, last case is having mutation in exon 7 of ABCC8 gene. all of them were still having recurrent hypoglycaemia hyperinsulimemia state despite the Sirolimus level reached the therapeutic level.
Conclusion: Although treatment of CHI with Sirolimus in the previous trials were successful, our cases with homozygous mutation of KCNJ11 and ABCC8 mutations failed to response to Sirolimus trial and it should probably not be used as the first line of medication until further experience and better understanding of its relative risks and benefits.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology