Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell

• Published in: Journal of pediatric endocrinology & metabolism : JPEM Vol. 24; no. 11-12; p. 1019
• Main Authors: Oçal, Gönül, Flanagan, Sarah E, Hacihamdioğlu, Bülent, Berberoğlu, Merih, Siklar, Zeynep, Ellard, Sian, Savas Erdeve, Senay, Okulu, Emel, Akin, Ilke Mungan, Atasay, Begum, Arsan, Saadet, Yağmurlu, Aydin
• Format: Journal Article
• Language: English
• Published: Germany 01-12-2011
• Subjects: Adolescent; ATP-Binding Cassette Transporters - genetics; Birth Weight - genetics; Child; Child, Preschool; Congenital Hyperinsulinism - genetics; Congenital Hyperinsulinism - physiopathology; Congenital Hyperinsulinism - therapy; Female; Genes, Dominant; Genes, Recessive; Humans; Insulin-Secreting Cells - physiology; KATP Channels - genetics; Male; Pedigree; Potassium Channels, Inwardly Rectifying - genetics; Receptors, Drug - genetics; Sulfonylurea Receptors; Treatment Outcome
• DOI: 10.1515/JPEM.2011.347
• ISSN: 0334-018X

Recessive mutations in ABCC8/KCNJ11 of beta-cell K(ATP) channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not.
We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited K(ATP) channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive K(ATP) channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH.
The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management.