Managing congenital hyperinsulinism: improving outcomes with a multidisciplinary approach

Abstract:

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in pediatric patients and is associated with significant risk of hypoglycemic seizures and developmental delays. CHI results from mutations in at least nine genes that play a role in regulating beta-cell insulin secretion. Thus, patients with CHI have dysregulated insulin secretion that is unresponsive to blood glucose level. Each different genetic etiology of CHI is associated with particular clinical characteristics that affect management decisions. Given the broad phenotypic spectrum and relatively rare prevalence of CHI, it is important that patients with CHI be evaluated by clinicians experienced with CHI and the multiple subspecialty services that are necessary for the management of the disorder. In this review, we summarize the pathophysiology and genetic causes of CHI and then focus primarily on the most common genetic cause (mutations in the ATP-gated potassium [K_ATP] channel) for further discussion of diagnosis, medical and surgical management, and potential acute and chronic complications. We provide insight from relevant published studies and reports, in addition to anecdotal information from our center’s clinical experience in caring for over 400 patients with CHI. Careful assessment of each patient’s individual pathophysiology is necessary to determine the appropriate treatment regimen, and continued close follow-up and monitoring of disease- and treatment-related complications are essential. Although significant improvements have been made in the past several years with regard to diagnosis and management, given the continued high morbidity rate in patients with CHI, improved diagnostic techniques and new therapeutic options would be welcomed.

Keywords::

• hypoglycemia
• hyperinsulinism
• beta-cell
• congenital
• monogenic

Acknowledgments

We thank the staff of the Congenital Hyperinsulinism Center at The Children’s Hospital of Philadelphia. Specifically, we thank Dr Charles A Stanley, Dr Diva D De León, Dr Katherine Lord, and Kara E Boodhansingh for their helpful discussions. We also thank the patients and families who have received care at our center.

Disclosure

AM Ackermann is supported by a grant from the Juvenile Diabetes Research Foundation (3-PDF-2014-186-A-N). AA Palladino reports no conflicts of interest in this work.