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Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management.
MedLine Citation:
PMID:  22231386     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Senthil Senniappan; Balasubramaniam Shanti; Chela James; Khalid Hussain
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-10
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  -     ISSN:  1573-2665     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Trust WC1N 3JH and the Institute of Child Health, University College London, London, WC1N 1EH, UK.
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