Sirolimus for the Treatment of Hyperinsulinism

Inclusion Criteria: 1. Males or females age ≥14 days to 12 months. 2. Confirmed diagnosis of hyperinsulinism. 3. Mutation analysis results demonstrating bi-allelic mutations in either ABCC8 or KCNJ11. 4. Failure to respond to maximal dose of diazoxide (15 mg/kg/day), if diazoxide is indicated. 1. Unable to wean intravenous dextrose after at least 3 days of diazoxide therapy and/or 2. Persistent hypoglycemia after at least 3 days of diazoxide therapy 5. High glucose infusion rate requirement (greater or equal to 10 mg/kg/min). 6. Parental/guardian permission (informed consent). Exclusion Criteria: 1. Infants with suspected or confirmed focal hyperinsulinism who are candidates for surgical resection 2. Current therapy with diazoxide. Subjects may be eligible for participation 48 hrs after discontinuation of diazoxide. 3. Laboratory abnormalities that indicate clinically significant hematologic, hepatobiliary, or renal disease: 1. AST/SGOT \> 2.5 times the upper limit of normal 2. ALT/SGPT \> 2.5 times the upper limit of normal 3. Total bilirubin \> 2.5 times the upper limit of normal 4. Hemoglobin \< 9 gm/dL 5. White blood cell count \< 3,000/ mm3 6. Platelet count \< 100,000/mm3 7. Creatinine \> 2.5 times the upper limit of normal 4. Evidence of active infection. 5. Evidence of cardiac or respiratory failure. 6. Known immune deficiency. 7. Preterm (\< 37 week gestation at birth). 8. Treatment with immunosuppressants. 9. Treatment with any drug known to interact significantly with sirolimus (strong inducers and strong inhibitors of CYP3A4 and P-gp with risk category D and X) including: Cyclosporine, clozapine, conivaptan, crizotinib, dabrafenib, dipyrone, boceprevir, echinacea, efavirenz, enzalutamide, fluconazole, fosphenytoin, fusidic acid, idelalisib, leflunomide, lomitapide, mifepristone, mitotane, natalizumab, nelfinavir, phenytoin, pimecrolimus, pimozide, posaconazole, roflumilast, St Johns Wort, stiripentol, tacrolimus, telaprevir, tofacitinib, rifampin, rifabutin, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin 10. Any investigational drug use within 5 half-lives of the drug prior to initiation of therapy. Subjects who had participated in other investigational drug studies will be eligible to participate after 5 half-lives from the last dose of the investigational agent and have recovered from acute investigational agent associated toxicity 11. History of surgical procedure within 8 weeks of enrollment. 12. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.