Mutations in the sulfonylurea receptor gene in relation to the long-term outcome of persistent hyperinsulinemic hypoglycemia of infancy

Background: A 95% pancreatectomy has become the mainstay of surgical therapy for patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) who did not respond to medical therapy. However, a high incidence of diabetes recently has been reported after a 95% pancreatectomy. Mutations of the SUR1 (sulfonylurea receptor) or Kir 6.2 (inwardly rectifying potassium channel) genes also have been detected in some patients with nesidioblastosis. Methods: Six infants underwent a subtotal pancreatectomy (about 80%) for the initial surgical treatment of PHHI between 1 and 6 months of age. The clinical follow-up ranged from 2 years to 23 years (mean, 14 years). Mutations of the SUR1 and Kir 6.2 genes were examined in whole exons by the PCR-SSPC method using DNA extracted from white blood cells. Results: SUR1 mutations were found in 5 of the 6 cases (83.3%), whereas no Kir 6.2 mutations were detected. Four of the 5 cases were found to have hetero-type mutations. These 4 cases and the 1 case without mutation were a pathologically focal type (head, 1; body, 2; tail, 2) and showed euglycemia after the operation. The other case was found to have a homo-type mutation and was pathologically diffuse. This case showed hypoglycemia and required medical treatment for several years. Diabetes developed 10 years after surgery. Conclusions: In the patients with either a hetero-type mutation or no mutation of the SUR1 gene, a focal type is suspected, whereas a homo-type mutation is considered to be associated with a diffuse type and also is a predictor of poor blood sugar control and a tendency toward diabetes. A genetic analysis of the SUR1 gene using peripheral white blood cells is considered a useful parameter to determine the optimal surgical strategy for the treatment of PHHI.