MC4R and hyperinsulinemic hypoglycemia, familial, 4: Carriers of variants that disrupt one or more of these mechanisms share the clinical features of MC4R deficiency reported by us and others (Farooqi et al., 2003; Lubrano-Berthelier et al., 2006; Table S2), demonstrating that these mechanisms act as control points to alter melanocortin tone to a level that is physiologically relevant in humans.