Congenital Hyperinsulinism Associated With Beckwith Wiedemann Syndrome

Abstract

J. D. is a 9-month-old Caucasian male with hyperinsulinism (HI). J. D. reportedly had hypoglycemia at birth (exact data unavailable). He was discharged day of life (DOL) 3, when blood glucose (BG) levels “stabilized.” On DOL 4, he had a seizure, was taken to the emergency room, and had a dangerously low BG level of 6 mg/dL (70–110). His medical evaluation was consistent with HI, but he failed medication therapy. He was discharged home on continuous feeds, but over the next several months had persistent hypoglycemia with BGs less than 50 mg/dL. Therefore, he was readmitted to his local hospital. Without additional treatment options, he was transferred to a hyperinsulinism center for further evaluation. J. D. was the product of a pregnancy complicated by maternal lupus. He was full term and weighed 4.6 kg (large for gestational age). HI was confirmed when laboratory values revealed a detectable insulin level, suppressed serum beta-hydroxybutyrate, and an inappropriate glycemic response to glucagon at the time of hypoglycemia. HI genetic testing was negative. An 18 F-DOPA PET scan of the pancreas suggested a possible focal lesion in the pancreatic head causing HI. During exploratory surgery, there was no evidence of focal or diffuse HI. The pathology of J. D.'s pancreatic biopsies indicated diffuse islet cell hyperplasia. J. D. had hemihypertrophy, raising the suspicion of Beckwith Wiedemann syndrome (BWS). Mosaic BWS was diagnosed, with a mutation on chromosome 11 (11p15.5p11.11). A gastrostomy tube was placed for continuous enteral administration of dextrose. J. D. maintained BGs greater than 70 mg/dL for 12 hours on a glucose infusion rate of 5 mg/kg per minute. He was discharged home on this regimen. BWS is frequently associated with HI. The clinical course and response to treatment have been variable, and medical therapy may not be successful. Further research is needed to analyze this association and treatment modalities. The genetic mutations in both HI and BWS are on chromosome 11, raising the question of a genetic link. Alternatively, because BWS is an overgrowth syndrome, perhaps the HI is simply an effect of islet cell hyperplasia.