The effectiveness of Sirolimus treatment in two rare disorders with nonketotic hypoinsulinemic hypoglycemia: The role of mTOR pathway

“Nonketotic-hypoinsulinemic hypoglycemia (NkHH)” is a very rare problem of glucose consumption increase without hyperinsulinism. This disorder has mainly been reported in cases with mutation and rarely in cases with mutation. In cases with or mutation, no effective therapy has been implemented in addition to frequent feeding to counter hypoglycemia. mTOR inhibitor Sirolimus has been used in hyperinsulinemic hypoglycemia that was unresponsive to other medical treatment. In insulin signaling pathway, both and play a role before mTOR. However, the role of Sirolimus on hypoglycemia in and mutations is unknown. Case 1: Six monts old female with mutation (c.49G>A (p.E17K) has showed NkHH. Frequent feeding was unsuccesful for treating the hypoglycemia and proptosis has been getting worse. Sirolimus treatment has been started at 3 years of age. Resultantly, blood glucose (BG) levels have been increased to normal levels. Case 2: In a male case with mutation (p.G132V (c.395G>T), Persistent NkHH has appeared at 16 years of age (fasting BG: 27 mg/dl, fasting insulin1.5 mmol/L, while ketone negative). Sirolimus treatment was started and hypoglycemia was succesfully controlled. NkHH is a very rare and significant disorder which provided some challanges in both diagnosis and treatment. Additionally, and also mutations could lead to NkHH. Sirolimus treatment, by mTOR inhibition, appeared to be effectively controlling the peristent hypoglycemia and could be a lifesaving tool for these kind of disorders.