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01-07-2012 | Review

Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management

Authors: Senthil Senniappan, Balasubramaniam Shanti, Chela James, Khalid Hussain

Published in: Journal of Inherited Metabolic Disease | Issue 4/2012

Abstract

Hyperinsulinaemic hypoglycaemia (HH) is due to the unregulated secretion of insulin from pancreatic β-cells. A rapid diagnosis and appropriate management of these patients is essential to prevent the potentially associated complications like epilepsy, cerebral palsy and neurological impairment. The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion. The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell K_ATP channel. At a histological level there are two major forms (diffuse and focal) each with a different genetic aetiology. The diffuse form is inherited in an autosomal recessive (or dominant) manner whereas the focal form is sporadic in inheritance and is localised to a small region of the pancreas. The focal form can now be accurately localised pre-operatively using a specialised positron emission tomography scan with the isotope Fluroine-18L-3, 4-dihydroxyphenyalanine (18F-DOPA-PET). Focal lesionectomy can provide cure from the hypoglycaemia. However the diffuse form is managed medically or by near total pancreatectomy (with high risk of diabetes mellitus). Recent advances in molecular genetics, imaging with 18F-DOPA-PET/CT and novel surgical techniques have changed the clinical approach to patients with HH.

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Title: Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management
Authors: Senthil Senniappan
Balasubramaniam Shanti
Chela James
Khalid Hussain
Publication date: 01-07-2012
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 4/2012
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-011-9441-2

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