Several lines of evidence lent strong support to NOS uncoupling as a potential mechanism contributing to the NOS dysfunction which includes a state of BH4 deficiency, blunting of NO generation upon stimulation by agonists, decrease in total NOS activity, increase in lipid peroxidation levels, upregulation of eNOS protein expression and enhancement of eNOS and nNOS monomerization. The gene discussed is NOS3; the disease is hyperinsulinemic hypoglycemia, familial, 4.