Clinical and enzymatic phenotypes in congenital hyperinsulinemic hypoglycemia due to glucokinase-activating mutations: A report of two cases and a brief overview of the literature.
Mutations in the GCK gene lead to different forms of glucokinase (GCK)-disease, activating mutations cause hyperinsulinaemic hypoglycaemia while inactivating mutations cause monogenic diabetes.
Biochemical and structural analysis of this loop variant and GCK variants associated with hyperinsulinemic hypoglycemia reveal two distinct mechanisms of enzyme activation.
Heterozygous inactivating mutations in glucokinase cause maturity-onset diabetes of the young (MODY), homozygous inactivating in glucokinase mutations result in permanent neonatal diabetes whereas heterozygous activating glucokinase mutations cause hyperinsulinaemic hypoglycaemia.
Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.
Heterozygous inactivating mutations in the glucokinase gene (GCK) cause a mild form of diabetes (maturity-onset diabetes of the young [MODY]2), and activating mutations have been associated with a mild form of familial hyperinsulinemic hypoglycemia.
Biochemical genetic studies have characterized many activating and inactivating GK mutants that have been discovered in patients with hyperinsulinemic hypoglycemia or diabetes, all inherited as autosomal dominant traits.
An activating mutation in the "glucose sensor" glucokinase has recently been reported in one family with diazoxide-responsive autosomal dominant hyperinsulinemic hypoglycemia.
Clinical data for maturity onset diabetes of the young type linked to the glucokinase gene and familial hyperinsulinaemic hypoglycaemia linked to the glucokinase gene and the glucokinase kinetic data of this study were used to test the model.