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. 2013 Jan;17(1):19-30.
doi: 10.4103/2230-8210.107822.

The molecular mechanisms, diagnosis and management of congenital hyperinsulinism

Senthil Senniappan  1 , Ved Bhushan Arya, Khalid Hussain
Affiliations

The molecular mechanisms, diagnosis and management of congenital hyperinsulinism

Senthil Senniappan et al. Indian J Endocrinol Metab. 2013 Jan.

Abstract

Congenital hyperinsulinism (CHI) is the result of unregulated insulin secretion from the pancreatic β-cells leading to severe hypoglycaemia. In these patients it is important to make an accurate diagnosis and initiate the appropriate management so as to avoid hypoglycemic episodes and prevent the potentially associated complications like epilepsy, neurological impairment and cerebral palsy. At a genetic level abnormalities in eight different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) have been reported with CHI. Loss of function mutations in ABCC8/KCNJ11 lead to the most severe forms of CHI which are usually medically unresponsive. At a histological level there are two major subgroups, diffuse and focal, each with a different genetic etiology. The focal form is sporadic in inheritance and is localized to a small region of the pancreas whereas the diffuse form is inherited in an autosomal recessive (or dominant) manner. Imaging using a specialized positron emission tomography scan with the isotope fluroine-18 L-3, 4-dihydroxyphenyalanine (18F-DOPA-PET-CT) is used to accurately locate the focal lesion pre-operatively and if removed can cure the patient from hypoglycemia. Understanding the molecular mechanisms, the histological basis, improvements in imaging modalities and surgical techniques have all improved the management of patients with CHI.

Keywords: Diazoxide; hyperinsulinism; hypoglycemia.

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Conflict of interest statement

Conflict of Interest: No

Figures

Figure 1
Figure 1
Common mutations associated with CHI. (1) ATP gated K+ channel (KATP) encoded by ABCC8 and KCNJ11; (2) Glutamate Dehydrogenase (GDH) encoded by GLUD1; (3) Glucokinase (GCK) encoded by GCK gene; (4) L-3-hyroxyacyl-coenzyme A dehydrogenase (HADH) encoded by HADH; (5) Hepatocyte Nuclear Factor 4α (HNF4α) encoded by HNF4A gene; (6) The moncarboxylate transporter (MCT1) encoded by SLC16A1; (7) Uncoupling Protein 2 (UCP2)
Figure 2
Figure 2
Outline of the suggested diagnostic and management cascade of patients presenting with CHI. The assessment of the response to diazoxide is critical in terms of planning further investigations
See this image and copyright information in PMC

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