ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume: 16 Issue: 1 Year: 2024
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Turkish Society for Pediatric Endocrinology and Diabetes
A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2016; 8(4): 478-481 | DOI: 10.4274/jcrpe.2773

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

Sevim Ünal1, Deniz Gönülal1, Ahmet Uçaktürk2, Betül Siyah Bilgin1, Sarah E. Flanagan3, Fatih Gürbüz2, Meltem Tayfun2, Selin Elmaoğulları2, Aslıhan Araslı2, Fatma Demirel4, Sian Ellard3, Khalid Hussain4
1Ankara Children’S Hematology-Oncology Training And Research Hospital, Clinic Of Neonatology, Ankara, Turkey
2Ankara Children’S Hematology-Oncology Training And Research Hospital, Clinic Of Pediatric Endocrinology And Metabolism, Ankara, Turkey
3University Of Exeter Medical School, Biomedical And Clinical Science, Exeter, United Kingdom
4University College London, Department Of Pediatric Endocrinology, London, United Kingdom

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.

Keywords: congenital hyperinsulinism,newborn,persistent hypoglycemia,sirolimus

Sevim Ünal, Deniz Gönülal, Ahmet Uçaktürk, Betül Siyah Bilgin, Sarah E. Flanagan, Fatih Gürbüz, Meltem Tayfun, Selin Elmaoğulları, Aslıhan Araslı, Fatma Demirel, Sian Ellard, Khalid Hussain. A Novel Homozygous Mutation in the KCNJ11 Gene of a Neonate with Congenital Hyperinsulinism and Successful Management with Sirolimus. J Clin Res Pediatr Endocrinol. 2016; 8(4): 478-481
Manuscript Language: English
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