Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist

Absence of proopiomelanocortin results in early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism. Two affected patients received setmelanotide, a new melanocortin-4 receptor agonist, which led to sustainable reduction of hunger and substantial weight loss. Melanocyte-stimulating hormone, which is produced from proopiomelanocortin, plays a pivotal role in the regulation of satiety and energy expenditure. In the hypothalamic leptin–melanocortin signaling pathway, melanocyte-stimulating hormone transmits the anorexic effect of leptin through the melanocortin-4 receptor. 1 Patients with a mutation in the gene encoding proopiomelanocortin ( POMC ), a very rare condition, have early-onset obesity due to severe hyperphagia as a result of the lack of hypothalamic melanocyte-stimulating hormone. Furthermore, the lack of melanocyte-stimulating hormone at the melanocortin-1 receptor in melanocytes and hair follicles may lead to pale skin and red hair. In addition, affected persons have secondary hypocortisolism . . .