Characterization of the ABCC8 gene mutation and phenotype in patients with congenital hyperinsulinism in western Saudi Arabia

Objectives: To understand the genetic etiologies of congenital hyperinsulinism (CHI) in a population of Saudi patients, and to explore genotype-phenotype characteristics. Methods: We retrospectively reviewed a cohort of 11 children with CHI presenting to King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between March 2007 and February 2012. Mutational analysis (ABCC8 and KCNJ11) was performed retrospectively to identify phenotype and genotype characteristics. Results: Analysis revealed ABCC8 mutations in 81.8\% (9/11) of patients, with 2 patients not revealing any gene mutation. All positive patients showed a homozygous mutation in the ABCC8 gene, one in exon 29, 2 in exon 1-22, 2 in exon 28, and 4 in intron 36; one patient had a heterozygous mutation. Five patients (45.4\%) responded well to treatment with diazoxide not requiring subtotal pancreatectomy, while 6 patients (54.6\%) required subtotal pancreatectomy despite treatment with diazoxide and octreotide. Three patients (33.3\%) died while waiting for surgery due to sepsis and thrombosis. Two patients (18.1\%) showed remission, one of them after subtotal pancreatectomy. Conclusion: Homozygous mutations in ABCC8 are the most common causes of CHI in Saudi patients. Early diagnosis and therapy for persistent hyperinsulinemic hypoglycemia of infancy are essential to prevent neurodevelopmental delay.