GCK and MODY: The inactivating GCK nonsynonymous substitutions cause maturity-onset diabetes of the young (GCK-MODY) or insulin-deficient hyperglycemia when only one allele is affected, and they cause severe permanent neonatal diabetes mellitus (PNDM) when both alleles are inactivated, whereas the activating nonsynonymous substitutions lead to persistent hyperinsulinemic hypoglycemia of infancy (PHHI).