Congenital Hyperinsulinism due to a Compound Heterozygous ABCC8 Mutation with Spontaneous Resolution at Eight Weeks

• Published in: Hormone research in paediatrics Vol. 73; no. 4; pp. 287 - 292
• Main Authors: Kumaran, Anitha, Kapoor, Ritika R., Flanagan, Sarah E., Ellard, Sian, Hussain, Khalid
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2010
• Subjects: ATP-Binding Cassette Transporters - genetics; Congenital Hyperinsulinism - blood; Congenital Hyperinsulinism - genetics; Congenital Hyperinsulinism - pathology; DNA - chemistry; DNA - genetics; Humans; Hypoglycemia - blood; Hypoglycemia - genetics; Hypoglycemia - pathology; Infant, Newborn; Male; Mutation, Missense; Novel Insights from Clinical Practice; Parents; Pedigree; Polymerase Chain Reaction; Potassium Channels, Inwardly Rectifying - genetics; Receptors, Drug - genetics; Sulfonylurea Receptors; Hypoglycaemia; Hyperinsulinism; Glucose
• ISSN: 1663-2818; 1663-2826
• DOI: 10.1159/000284394

Background: Recessive inactivating mutations in ABCC8 and KCNJ11 (which encode the two subunits of the adenosine triphosphate-sensitive potassium (KATP) channels in β-cells) are the most common cause of medically unresponsive congenital hyperinsulinism (CHI) which requires a near-total pancreatectomy. Methods/Results: A patient born at term with marked macrosomia (5,900 g) presented at the age of 2 h with severe hyperinsulinaemic hypoglycaemia. He failed to respond to treatment with the KATP agonist, diazoxide. An 18F DOPA-PET scan showed intense diffuse uptake of 18F DOPA (consistent with diffuse disease) and genetic analysis of the ABCC8 gene confirmed a compound heterozygote missense ABCC8 mutation (R168C/S606T). However, unexpectedly in this patient the hyperinsulinaemic hypoglycaemia started to improve spontaneously at 7 weeks of age prior to planned pancreatic surgery. Conclusions: This is the first report of a patient with clinically severe autosomal-recessive diffuse CHI due to a compound heterozygous ABCC8 mutation that has resulted in spontaneous resolution at such an early age. Compound heterozygote ABCC8 mutations result in complex interactions, and it is possible that this interaction may modify the potential disease pathogenesis. It is important that physicians are aware of this unusual outcome in order to avoid unnecessary early pancreatic surgery with potential life-long implications.