title: A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus.
abstract: 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.
authors.affiliation: Ankara Children's Hematology-Oncology Training and Research Hospital, Clinic of Neonatology, Ankara, Turkey, Phone: +90 312 596 97 30 E-mail: sevimunal@yahoo.com.
authors.forename: Sevim
authors.initials: S
authors.lastname: Ünal
authors.forename: Deniz
authors.initials: D
authors.lastname: Gönülal
authors.forename: Ahmet
authors.initials: A
authors.lastname: Uçaktürk
authors.forename: Betül
authors.initials: B
authors.lastname: Siyah Bilgin
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Fatih
authors.initials: F
authors.lastname: Gürbüz
authors.forename: Meltem
authors.initials: M
authors.lastname: Tayfun
authors.forename: Selin
authors.initials: S
authors.lastname: Elmaoğulları
authors.forename: Aslıhan
authors.initials: A
authors.lastname: Araslı
authors.forename: Fatma
authors.initials: F
authors.lastname: Demirel
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D044903:Congenital Hyperinsulinism / Q000188:drug therapy* / Q000235:genetics; D003241:Consanguinity; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010290:Parents; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D020123:Sirolimus / Q000627:therapeutic use*; D016896:Treatment Outcome; D000099161:Kcnj11 Channel
chemical_list: D007166:Immunosuppressive Agents; D024661:Potassium Channels, Inwardly Rectifying; D020123:Sirolimus; D000099161:Kcnj11 Channel