ESPE Abstracts

Case Report: A preterm boy was born at 35 weeks gestational age by cesarean section due to fetal macrossomia and polyhydramnios, weight 4980g (4.3 SDS, Intergrowth 21st), length 53cm (3.1 SDS), 1-min-Apgar 2. He needed resuscitation after birth, and his glycemia was 20 mg/dL. At the Neonatal Intensive Care Unit (NICU), he presented with severe hypoglycemia (10mg/dL) and required intravenous glucose infusion rate (GIR) 10mg/kg/min that increased progressively up to 21mg/kg/min. At critical blood sample, glycemia was 7 mg/dL, insulin 57.2 uIU/mL, and cortisol 28.2 mg/dL; 30 min after glucagon (0.5 mg i.v.), glycemia was 22mg/dL and insulin, 9.17 uIU/mL. At 13 days of age, somatropin (0.1 mg/kg/day) and prednisolone (15mg/m²/day) were started, as counter regulatory hormones of insulin. At 21 days of age, diazoxide was initiated, with doses increased up to 20 mg/kg/day, with no improvement. It was replaced by continuous i.v. octreotide, dose gradually increased up to 35mcg/kg/day. At 2 months of age, octreotide was fractionated into three daily subcutaneous doses. Good control of hypoglycemic episodes was obtained at 2.6 months, with GIR reduction. Patient discharged at 5 months, with octreotide 34mcg/kg/day, somatropin 0.1 mg/kg/day and prednisolone 10 mg/m²/day. During follow-up over the first four years of life, patient presented with few severe symptomatic episodes of hypoglycemia. Currently, he is 4.3 years old, height 114.8cm (+2.0 SDS, WHO), weight 24 kg (+2.6 SDS). The neuropsychomotor development was delayed, particularly language development. Whole-exome sequencing identified probable heterozygous pathogenic in the ABCC8 gene, position chr11:17424233 (p.Glu1208del).

Discussion: The ABCC8 gene codes the sulfonylurea receptor (SUR1), a subunit of the ATP-dependent potassium channels expressed in beta pancreatic cells. Gene inactivating mutations in this gene promote excessive insulin secretion. Diazoxide acts directly on the SUR1 receptor and is recommended as first-line treatment for congenital hyperinsulinism, but patients with ABCC8 gene mutation usually do not respond to the drug. Somatostatin analogues, such as octreotide, are recommended to control episodes of hypoglycemia. The aim of treatment in children consists in maintaining serum glycemia over 70 mg/dL. Neurogenic and neuroglycopenic symptoms generally occur when plasma glucose concentration is reduced to 50 to 70 mg/dL. Persistent hypoglycemia, particularly over the neonatal period, results in impaired neurodevelopment.

Conclusion: Congenital hyperinsulinism is a high morbidity condition with few therapeutic options. Early diagnosis and management are crucial to prevent irreversible neurological damage.