In this study of 500 patients with severe early-onset obesity, two new heterozygous missense mutations in a region of POMC N terminus (C28F and L37F) were identified; these mutations were able to prevent POMC processing and thus the generation of bioactive products, suggesting a new molecular mechanism of human POMC deficiency [39]. Here, POMC is linked to hyperinsulinemic hypoglycemia, familial, 4.