Congenital hyperinsulinism: current status and future perspectives
Open Access
- 1 January 2014
- journal article
- review article
- Published by Korean Society of Pediatric Endocrinology in Annals of Pediatric Endocrinology & Metabolism
- Vol. 19 (2), 57-68
- https://doi.org/10.6065/apem.2014.19.2.57
Abstract
The diagnosis and treatment of congenital hyperinsulinism (CHI) have made a remarkable progress over the past 20 years and, currently, it is relatively rare to see patients who are left with severe psychomotor delay. The improvement was made possible by the recent developments in the understanding of the molecular and pathological basis of CHI. Known etiologies include inactivating mutations of the KATP channel genes (ABCC8 and KCNJ11) and HNF4A, HNF1A, HADH, and UCP2 or activating mutations of GLUD1, GCK, and SLC16A1. The understanding of the focal form of KATP channel CHI and its detection by 18F-fluoro-L-DOPA positron emission tomography have revolutionized the management of CHI, and many patients can be cured without postoperative diabetes mellitus. The incidence of the focal form appears to be higher in Asian countries; therefore, the establishment of treatment systems is even more important in this population. In addition to diazoxide or long-term subcutaneous infusion of octreotide or glucagon, long-acting octreotide or lanreotide have also been used successfully until spontaneous remission. Because of these medications, near-total pancreatectomy is less often performed even for the diazoxide-unresponsive diffuse form of CHI. Other promising medications include pasireotide, small-molecule correctors such as sulfonylurea or carbamazepine, GLP1 receptor antagonists, or mammalian target of rapamycin inhibitors. Unsolved questions in this field include the identification of the remaining genes responsible for CHI, the mechanisms leading to transient CHI, and the mechanisms responsible for the spontaneous remission of CHI. This article reviews recent developments and hypothesis regarding these questionsKeywords
This publication has 101 references indexed in Scilit:
- Whole Genome SNP Genotyping and Exome Sequencing Reveal Novel Genetic Variants and Putative Causative Genes in Congenital HyperinsulinismPLOS ONE, 2013
- Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital HyperinsulinismFrontiers in Endocrinology, 2013
- Impact of Oxidative Stress in Fetal ProgrammingJournal of Pregnancy, 2012
- The Value of Radiologic Interventions and 18F-DOPA PET in Diagnosing and Localizing Focal Congenital Hyperinsulinism: Systematic Review and Meta-AnalysisMolecular Imaging & Biology, 2012
- Pancreatic head resection and Roux-en-Y pancreaticojejunostomy for the treatment of the focal form of congenital hyperinsulinismJournal of Pediatric Surgery, 2012
- Congenital hyperinsulinism: current trends in diagnosis and therapyOrphanet Journal of Rare Diseases, 2011
- Genome-Wide Homozygosity Analysis Reveals HADH Mutations as a Common Cause of Diazoxide-Responsive Hyperinsulinemic-Hypoglycemia in Consanguineous PedigreesJournal of Clinical Endocrinology & Metabolism, 2011
- Mutations in UCP2 in Congenital Hyperinsulinism Reveal a Role for Regulation of Insulin SecretionPLOS ONE, 2008
- Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutationsJCI Insight, 2008
- Macrosomia and Hyperinsulinaemic Hypoglycaemia in Patients with Heterozygous Mutations in the HNF4A GenePLoS Medicine, 2007