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.
Taguchi
Tomoaki
T
Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, and Department of Clinical Examination, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Suita
Sachiyo
S
Ohkubo
Kumiko
K
Ono
Junko
J
D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D007003:Hypoglycemia / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation; D010179:Pancreas / Q000473:pathology / Q000601:surgery; D010180:Pancreatectomy; D010182:Pancreatic Diseases / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D016896:Treatment Outcome
C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors