Prematurity, Macrosomia, Hyperinsulinaemic Hypoglycaemia and a Dominant ABCC8 Gene Mutation

BMJ Case Rep. 2013 Apr 5;2013:bcr2013008767. doi: 10.1136/bcr-2013-008767.

Abstract

Congenital hyperinsulinism (CHI) is a rare cause of hyperinsulinaemic hypoglycaemia (HH) and is due to an inappropriate secretion of insulin by the pancreatic β-cells. Genetic defects in key genes lead to dysregulated insulin secretion and consequent hypoglycaemia. Mutations in the genes ABCC8/KCNJ11, encoding SUR1/Kir6.2 components of the K(ATP) channels, respectively, are the commonest cause of CHI. A 33(+6) week gestation male infant weighing 3.38 kg (above 90th centile) presented with severe neonatal symptomatic hypoglycaemia. He required a glucose infusion rate of 20 mg/kg/min to maintain normoglycaemia (blood glucose levels at >3.5 mmol/l). Investigations established the diagnosis of HH (blood glucose 2.2 mmol/l with simultaneous insulin of 97.4 mU/l). Subsequent molecular genetic studies identified a heterozygous pathogenic ABCC8 missense mutation, p.R1353H (c.4058G>A), inherited from an unaffected mother. His HH was diazoxide responsive and resolved within 3 months of life.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Antihypertensive Agents / therapeutic use
  • Chlorothiazide / therapeutic use
  • Congenital Hyperinsulinism / drug therapy
  • Congenital Hyperinsulinism / genetics*
  • Diazoxide / therapeutic use
  • Fetal Macrosomia / genetics*
  • Glucose / therapeutic use
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Male
  • Mutation
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Receptors, Drug / genetics*
  • Sulfonylurea Receptors

Substances

  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Antihypertensive Agents
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Chlorothiazide
  • Glucose
  • Diazoxide