title: Prematurity, macrosomia, hyperinsulinaemic hypoglycaemia and a dominant ABCC8 gene mutation.
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.
authors.affiliation: Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Dana
authors.initials: D
authors.lastname: Khoriati
authors.forename: Ved Bhushan
authors.initials: VB
authors.lastname: Arya
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002740:Chlorothiazide / Q000627:therapeutic use; D044903:Congenital Hyperinsulinism / Q000188:drug therapy / Q000235:genetics*; D003981:Diazoxide / Q000627:therapeutic use; D005320:Fetal Macrosomia / Q000235:genetics*; D005947:Glucose / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors
chemical_list: C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D000959:Antihypertensive Agents; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D002740:Chlorothiazide; D005947:Glucose; D003981:Diazoxide
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