Diagnosis of ABCC8 congenital hyperinsulinism of infancy in a 20 year-old man evaluated for factitious hypoglycemia

Context: Hypoglycemia is a rare event in healthy adults, and the differential diagnosis includes many diseases some of which are rare and easily missed. Description of the case: A 20 year-old male military paramedic was referred to our Emergency Department for the investigation of recurrent hypoglycemia episodes during the last months. Factitious hypoglycemia was excluded and organic hyperinsulinemic hypoglycemia was diagnosed by prolonged fast. Imaging studies (endoscopic ultrasound and triple-phase computed tomography) were normal. Before additional diagnostic tests or exploratory surgery were performed, a deeper interrogation of the patient and his family revealed events compatible with episodes of hypoglycemia since childhood. Moreover, a single event of hypoglycemia during childhood was documented in one brother, suggesting the possibility of an inborn inherited metabolic disease. As the patient was Ashkenazi Jewish, we suspected the presence of one of two common founder mutations in the ABCC8 gene, which codes for one subunit of the β-cell ATP sensitive potassium channel, known to cause congenital hyperinsulinism of infancy. Direct sequencing indeed revealed homozygousity for the ABCC8 gene mutation 3989–9 G>A. Conclusion: The differential diagnosis of hyperinsulinemic hypoglycemia in a young healthy adult should include genetic disorders of glucose homeostasis. In the Ashkenazi population, rapid and inexpensive screening for two founder mutations can confirm the diagnosis, avoiding expensive, invasive and potentially dangerous diagnostic procedures.