Molecular mechanisms of neonatal hyperinsulinism.

Details

Serval ID
serval:BIB_8F533674418C
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Molecular mechanisms of neonatal hyperinsulinism.
Journal
Hormone Research
Author(s)
Giurgea I., Bellanné-Chantelot C., Ribeiro M., Hubert L., Sempoux C., Robert J.J., Blankenstein O., Hussain K., Brunelle F., Nihoul-Fékété C., Rahier J., Jaubert F., de Lonlay P.
ISSN
0301-0163 (Print)
ISSN-L
0301-0163
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
66
Number
6
Pages
289-296
Language
english
Notes
Publication types: Journal Article ; ReviewPublication Status: ppublish
Abstract
Congenital hyperinsulinism (CHI), characterized by profound hypoglycaemia related to inappropriate insulin secretion, may be associated histologically with either diffuse insulin hypersecretion or focal adenomatous hyperplasia, which share a similar clinical presentation, but result from different molecular mechanisms. Whereas diffuse CHI is of autosomal recessive, or less frequently of autosomal dominant, inheritance, focal CHI is sporadic. The most common mechanism underlying CHI is dysfunction of the pancreatic ATP-sensitive potassium channel (K(+)(ATP)). The two subunits of the K(+)(ATP) channel are encoded by the sulfonylurea receptor gene (SUR1 or ABCC8) and the inward-rectifying potassium channel gene (KIR6.2 or KCNJ11), both located in the 11p15.1 region. Germ-line, paternally inherited, mutations of the SUR1 or KIR6.2 genes, together with somatic maternal haplo-insufficiency for 11p15.5, were shown to result in focal CHI. Diffuse CHI results from germ-line mutations in the SUR1 or KIR6.2 genes, but also from mutations in several other genes, namely glutamate dehydrogenase (with associated hyperammonaemia), glucokinase, short-chain L-3-hydroxyacyl-CoA dehydrogenase, and insulin receptor gene. Hyperinsulinaemic hypoglycaemia may be observed in several overlapping syndromes, such as Beckwith-Wiedemann syndrome (BWS), Perlman syndrome, and, more rarely, Sotos syndrome. Mosaic genome-wide paternal isodisomy has recently been reported in patients with clinical signs of BWS and CHI. The primary causes of CHI are genetically heterogeneous and have not yet been completely unveiled. However, secondary causes of hyperinsulinism have to be considered such as fatty acid oxidation deficiency, congenital disorders of glycosylation and factitious hypoglycaemia secondary to Munchausen by proxy syndrome.
Keywords
ATP-Binding Cassette Transporters/genetics, Chromosomes, Human, Pair 11/genetics, Congenital Hyperinsulinism/genetics, Congenital Hyperinsulinism/physiopathology, Genes, Dominant, Genes, Recessive, Glutamate Dehydrogenase/genetics, Humans, Infant, Infant, Newborn, Insulin/secretion, Loss of Heterozygosity, Potassium Channels/genetics, Potassium Channels, Inwardly Rectifying/genetics, Receptors, Drug/genetics, Sulfonylurea Receptors, Syndrome
Pubmed
Web of science
Open Access
Yes
Create date
20/10/2016 16:12
Last modification date
20/08/2019 14:53
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