A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus

摘要

Congenital hyperinsulinism (CHI) is the most common cause of neonatal persistent hypoglycemia caused by mutations in nine known genes. Early diagnosis and treatment are important to prevent brain injury. The clinical presentation and response to pharmacological therapy may vary depending on the underlying pathology. Genetic analysis is important in the diagnosis, treatment, patient follow-up, and prediction of recurrence risk within families. Our patient had severe hypoglycemia and seizure following birth. His diagnostic evaluations including genetic testing confirmed CHI. He was treated with a high-glucose infusion, high-dose diazoxide, nifedipine, and glucagon infusion. A novel homozygous mutation (p.F315I) in the KCNJ11 gene, leading to diazoxide-unresponsive CHI, was identified. Both parents were heterozygous for this mutation. Our patient’s clinical course was complicated by severe refractory hypoglycemia; he was successfully managed with sirolimus and surgical intervention was not required. Diazoxide, nifedipine, and glucagon were discontinued gradually following sirolimus therapy. The patient was discharged at 2 months of age on low-dose octreotide and sirolimus. His outpatient clinical follow-up continues with no episodes of hypoglycemia. We present a novel homozygous p.F315I mutation in the KCNJ11 gene leading to diazoxide-unresponsive CHI in a neonate. This case illustrates the challenges associated with the diagnosis and management of CHI, as well as the successful therapy with sirolimus.