Molecular mechanisms of neonatal hyperinsulinism

被引:38
作者
Giurgea, Irina
Bellanne-Chantelot, Christine
Ribeiro, Maria
Hubert, Laurence
Sempoux, Christine
Robert, Jean-Jacques
Blankenstein, Oliver
Hussain, Kahlid
Brunelle, Francis
Nihoul-Fekete, Claire
Rahier, Jacques
Jaubert, Francis
de Lonlay, Pascale
机构
[1] Hop Henri Mondor, INSERM, U654, FR-94010 Creteil, France
[2] Hop Henri Mondor, Dept Genet, FR-94010 Creteil, France
[3] Inst Child Hlth, London, England
[4] Great Ormond St Hosp Sick Children, Dept Pediat, London, England
[5] Charite, CVK OHC Kinderklin, Berlin, Germany
[6] Humboldt Univ, Dept Pediat, D-1086 Berlin, Germany
[7] Catholic Univ Louvain, Clin Univ St Luc, Dept Pathol, B-1200 Brussels, Belgium
[8] Hop Necker Enfants Malad, Dept Pediat, Paris, France
[9] Hop Necker Enfants Malad, Dept Radiol, Paris, France
[10] Hop Necker Enfants Malad, Dept Surg, Paris, France
[11] Hop Necker Enfants Malad, Dept Pathol, Paris, France
[12] CEA, Serv Hosp Frederic Joliot, INSERM, ERM 0205,DSV,DRM, F-91406 Orsay, France
关键词
neonatal hyperinsulinism; molecular mechanisms; hypoglycaemia; diffuse insulin hypersecretion; focal adenomatous hyperplasia;
D O I
10.1159/000095938
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 haploinsufficiency 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. Copyright (c) 2006 S. Karger AG,
引用
收藏
页码:289 / 296
页数:8
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