Purpose of review: To highlight advances in congenital hyperinsulinism (HI), including newly described molecular mechanisms of disease, novel therapeutic interventions, and improved understanding of long-term outcomes.
Recent findings: Important advances have been made elucidating the molecular mechanisms responsible for HI. Non-coding variants in HK1 have been found to cause aberrant hexokinase expression. Inactivating mutations in SLC25A36 have been identified in children with features of the hyperinsulinism hyperammonemia syndrome. Low-level mosaic mutations in known HI genes have been detected in cases of 'genetic testing negative' HI. Identification and localization of focal HI lesions remains a priority, since focal HI can be cured with surgery. Use of 68 Ga-NODAGA-exendin-4 PET has been proposed to localize focal lesions. Additional studies are needed before this technique replaces 18 F-DOPA PET as standard of care. Treatment options for children with diffuse HI remain limited. The long-acting somatostatin analog, lanreotide, was shown to significantly improve glycemic control in a large series of children with HI. New therapies are under development, with promising preliminary results. Long-term quality of life and neurodevelopmental outcomes remain suboptimal.
Summary: Advanced genetic and epigenomic analytic techniques have uncovered novel molecular mechanisms of HI. Development of new drugs holds promise to improve long-term outcomes for individuals with HI.
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