Congenital hyperinsulinism (HI) is the most common cause of persistent neonatal hypoglycemia. The natural history of HI varies by genotype, but in most cases, the severity and frequency of hypoglycemia ameliorates with age. Pharmacologic treatment is not needed beyond adolescence for most cases. We describe 3 individuals with HI due to activating variants in GCK who escaped diagnosis during childhood, presenting with symptomatic hypoglycemia as adults
Case 1: 26 yo woman who was found to have hypoglycemia on routine laboratory testing; plasma glucose (PG) of 45 mg/dL. For many years, recurrent nausea, and sweating were attributed to anxiety. Comprehensive testing revealed hyperinsulinemic hypoglycemia suspected to be from an insulinoma. Extensive imaging and surgical exploration didn't find a tumor. Genetic testing revealed a pathogenic, heterozygous, activating variant in glucokinase (GCK; c.1367C>T [p.Ala456Val]). Treatment with diazoxide and an investigational glucagon analogue reduced her hypoglycemia frequency and anxiety symptoms.
Case 2: 42 yo woman who was found to have PG 40 mg/dL during an evaluation for chest pain at 26 years of age. Limited diagnostic evaluation was consistent with hyperinsulinemic hypoglycemia suspected to be from an insulinoma. Imaging and exploratory surgery didn't find a tumor. After multiple failed attempts to find an insulinoma and several years of recurrent dizziness, nervousness, vertigo and anxiety, genetic testing for HI was obtained and revealed a variant of uncertain significance in GCK (c.538A>G [p.Asn180Asp]). Treatment with diazoxide has improved her hypoglycemia and symptoms.
Case 3: 24 yo man who was found to have hypoglycemia after routine laboratory evaluation, non-fasting PG of 40 mg/dL. In retrospect, he reported persistent lightheadedness, mental fog, and getting lost while driving. His sister was known to have GCK-HI, and through a research study, was found to carry the same variant in GCK (c.200A>T [p.Glu67Val]). Treatment with diazoxide improved his hypoglycemia and symptoms.