Congenital Hypoglycemia Disorders: New Aspects of Etiology, Diagnosis, Treatment and Outcomes: Highlights of the Proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia April 2016

Abstract

Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Congenital hyperinsulinism (HI) is the most common and severe cause of persistent hypoglycemia in neonates and children. Recent discoveries of the genetic causes of HI have improved our understanding of the pathophysiology, but its management is complex and requires the integration of clinical, biochemical, molecular, and imaging findings to establish the appropriate treatment according to the subtype. Here we present a summary of a recent international symposium on congenital hypoglycemia disorders with emphasis on novel molecular mechanisms resulting in HI, genetic diagnosis, overall approach to management, novel therapies under development, and current outcomes.

Keywords: hyperinsulinism; hypoglycemia; insulin; neonatal; pancreas.

Figure 1

Management approach to neonates, infants and children with hyperinsulinism. HI: hyperinsulinism, PG: plasma glucose. * Start diuretics to prevent fluid overload. ^#Avoid octreotide in premature babies and infants < 4–6 weeks of age because of the risk of necrotizing enterocolitis.

Figure 2

Schematic representation of the normal parent of origin-specific imprinted allelic expression of the BWS locus on 11p15.5. Expressed genes are noted with an arrow. The hyperinsulinism genes ABCC8 and KCNJ11 as well as INS and L23 are biallelically expressed, while CDKN1C, KCNQ1, IGF2 and H19 are imprinted. IC1 is methylated on the paternal allele resulting in paternal expression of IGF2 and unmethylated on the maternal allele resulting in maternal expression of H19. IC2 is methylated on the maternal allele resulting in KCNQ1 and CDKN1C expression and unmethylated on the paternal allele. IC: imprinting center; TEL: telemore; ABCC8: ATP-Binding Cassette, subfamily C, member 8; KCNJ11: Potassium Channel, inwardly rectifying, subfamily J, member 11; CDKN1C: Cyclin-Dependent Kinase inhibitor 1C; KCNQ1: Potassium Channel, voltage-gated, KQT-like subfamily, member 1; INS: insulin; IGF2: Insulin-like Growth Factor 2; L23: ribosomal protein L23-like.