Bridging the gaps: recent advances in diagnosis, care, and outcomes in congenital hyperinsulinism

Abstract

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 68Ga-NODAGA-exendin-4 PET has been proposed to localize focal lesions. Additional studies are needed before this technique replaces 18F-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.

Cardiometabolic Risk Assessment in a Cohort of Children and Adolescents Diagnosed with Hyperinsulinemia

“…The incidence of obesity in childhood is currently increasing, potentially leading to overt psychophysical issues during school age and several medical diseases in early adulthood [ 30 , 31 , 32 , 33 , 34 ]. In Italy, approximately 21.3% and 9.3% of school-aged children are classified as overweight and obese, respectively [ 34 ].…”

Proposed Screening for Congenital Hyperinsulinism in Newborns: Perspective from a Neonatal–Perinatal Medicine Group

“…Persistent hypoglycemia in CHI is due, in a majority of patients, to monogenic variants controlling β-cell insulin secretion, most commonly as a result of inactivating mutations of the K ATP channel genes, ABCC8 and KCNJ11, which encode for SUR1 and Kir6.2 channel subunits. About 20% of patients with CHI, however, have no known identified genetic etiology [19]. Since functional membrane β-cell K ATP channels are required for the normal regulation of insulin secretion, abnormal K ATP channels due to genetic variants lead to uncontrolled insulin secretion and persistent hypoglycemia.…”