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Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management

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  • Published:
Journal of Inherited Metabolic Disease

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 KATP 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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Authors and Affiliations

  1. 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

    Senthil Senniappan, Chela James & Khalid Hussain

  2. Metabolic Unit, Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia

    Balasubramaniam Shanti

  3. Developmental Endocrinology Research Group, Molecular Genetics Unit, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK

    Khalid Hussain

Authors
  1. Senthil Senniappan
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  2. Balasubramaniam Shanti
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  3. Chela James
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  4. Khalid Hussain
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Corresponding author

Correspondence to Khalid Hussain.

Additional information

Communicated by: Ertan Mayatepek

Competing interest: None declared.

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Senniappan, S., Shanti, B., James, C. et al. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. J Inherit Metab Dis 35, 589–601 (2012). https://doi.org/10.1007/s10545-011-9441-2

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  • DOI: https://doi.org/10.1007/s10545-011-9441-2

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