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Noninsulinoma pancreatogenous hypoglycaemia in adults — a spotlight on its genetics
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Abstract
Hyperinsulinaemic hypoglycaemia (HH) is also classically referred to as “nesidioblastosis”. Heterogeneous clinical manifestation of the disease causes risk of late diagnosis or even misdiagnosis. In infants and children, it can lead to serious and permanent damage to the central nervous system, which leads to the manifesting mental retardation. HH is characterised by unregulated insulin secretion from pancreatic β-cells. This effect has been correlated with nine genes: ABCC8, KCNJ11, GCK, GLUD-1, HADH1, SLC16A1, HNF4A, HNF1A, and UCP2. Mutations in these genes were found in approximately 48% of cases. The genetic background of the remaining cases is unknown. Understanding the genetic basis of familial hyperinsulinism has changed the early look at the disease. It has allowed for the differentiation of specific types of the disease. Depending on which of the nine disease-associated loci bears a pathogenic mutation, they differ in phenotype and pattern of inheritance. This review provides a brief overview of the genetic mechanisms of HH and its possible clinical presentations. (Endokrynol Pol 2015; 66 (4): 344–354)
Abstract
Hyperinsulinaemic hypoglycaemia (HH) is also classically referred to as “nesidioblastosis”. Heterogeneous clinical manifestation of the disease causes risk of late diagnosis or even misdiagnosis. In infants and children, it can lead to serious and permanent damage to the central nervous system, which leads to the manifesting mental retardation. HH is characterised by unregulated insulin secretion from pancreatic β-cells. This effect has been correlated with nine genes: ABCC8, KCNJ11, GCK, GLUD-1, HADH1, SLC16A1, HNF4A, HNF1A, and UCP2. Mutations in these genes were found in approximately 48% of cases. The genetic background of the remaining cases is unknown. Understanding the genetic basis of familial hyperinsulinism has changed the early look at the disease. It has allowed for the differentiation of specific types of the disease. Depending on which of the nine disease-associated loci bears a pathogenic mutation, they differ in phenotype and pattern of inheritance. This review provides a brief overview of the genetic mechanisms of HH and its possible clinical presentations. (Endokrynol Pol 2015; 66 (4): 344–354)
Keywords
nesidioblastosis; hyperinsulinemic hypoglycemia; genetics; familial hyperinsulinism
About this articleTitle
Noninsulinoma pancreatogenous hypoglycaemia in adults — a spotlight on its genetics
Journal
Issue
Article type
Review paper
Pages
344-354
Published online
2015-09-01
Page views
2334
Article views/downloads
3463
DOI
10.5603/EP.2015.0044
Pubmed
Bibliographic record
Endokrynol Pol 2015;66(4):344-354.
Keywords
nesidioblastosis
hyperinsulinemic hypoglycemia
genetics
familial hyperinsulinism
Authors
Aleksandra Gilis-Januszewska
Jakub Piątkowski
Anna Skalniak
Beata Piwońska-Solska
Joanna Nazim
Dorota Pach
Elwira Przybylik-Mazurek
Anna Sowa-Staszczak
Jerzy Starzyk
Alicja Hubalewska-Dydejczyk
