ESPE Abstracts

Introduction: The ABCC8 gene encodes the SUR1 subunit of the ATP-sensitive potassium channel (K-ATP) in pancreatic beta cells, a key pathway in insulin secretion. Mutations in this gene are associated with neonatal diabetes (ND), and congenital hyperinsulinism (CHI).

Description: Cases 1 and 2 Two male monozygotic twins, with no significant medical history, developed persistent non acidotic ketotic hyperglycaemia within the first 48 hours of life. Intravenous insulin was started. Gastrointestinal malformations and pancreatic autoantibodies were excluded. A missense mutation in the ABCC8 gene (c.2473C>T) was detected. On day 45, insulin was changed to a diluted subcutaneous perfusion. The dose was progressively reduced maintaining normoglycaemia, and at 4 months it was stopped. Oral glibenclamide was never started in an outpatient setting due to the difficulty of dispensing minimal doses to a remote distance. At 12 months, growth and development are adequate.

Case 3: A full-term newborn female started persistent hypoglycaemia on the first day of life. Pregnancy and delivery were uneventful and there were no syndromic dysmorphic features. Laboratory tests confirmed hyperinsulinism. Two mutations (missense c.2797C>T and splice site c.1631-2A>T) in the ABCC8 gene were identified. PET-FDOPA showed diffuse pancreatic uptake. She was unresponsive to diazoxide. Continuous subcutaneous octreotide was then initiated. At 5 months, a gastrostomy button was placed. At 24 months, growth and development are adequate. Due to moderate hepatic steatosis, therapy with dasiglucagon is being considered.

Case 4: A 4-month-old male, with no significant medical history, exclusively breastfed until the previous week, started episodes of prostration associated with nonketotic hypoglycaemia. Laboratory tests confirmed hyperinsulinism. A heterozygous missense mutation (c.1332G>T) in the ABCC8 gene was identified. He was unresponsive to diazoxide, and started on intravenous octreotide. Due to parental refusal of continuous subcutaneous infusion, it was replaced by monthly lanreotide. At 19 months, growth and development are adequate, and there are no hepatic complications. He is awaiting a PET-FDOPA scan.

Discussion: ND and CHI arising from mutations in the ABCC8 gene present significant therapeutic and normoglycaemic control challenges. In ND sulphonylureas provide an effective treatment in most cases and transient forms may require a continuous adaptation to progressive reduction of insulin and glibencalmide dosing. On the other hand, management of CHI represents a greater therapeutic challenge, typically in diffuse cases unresponsive to diazoxide, often requiring somatostatin analogs or even partial pancreatic resection.