Molecular mechanisms of congenital hyperinsulinism and prospective therapeutic targets

Abstract

Introduction: Congenital hyperinsulinism (CHI) is a rare condition which leads to unregulated insulin secretion causing hyperinsulinemic hypoglycemia. At present, genetic abnormalities in nine different genes have been described which lead to unregulated insulin secretion. Typically CHI presents in the newborn period but it can present in infancy and childhood. The hypoglycemia is usually severe and can lead to brain damage if not managed appropriately. At a histological level, there are two major subtypes of CHI, namely focal and diffuse. The management of diffuse CHI (DCHI) remains a real challenge.

Areas covered: This review provides an overview of the clinical characteristics of CHI, the known genetic causes, pancreatic histology, medical management and pharmacology of the medications currently in use.

Expert opinion: Until recently, most patients with DCHI required a near total pancreatectomy and nearly all of these patients then develop life-long diabetes mellitus. There is now intensive research focusing on developing medical therapies for children with DCHI, which includes mammalian target of rapamycin (sirolimus), and long acting somatostatin analogs.

Keywords:

• congenital hyperinsulinism
• genes
• hyperinsulinaemic hypoglycaemia
• insulin

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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