These genetic deficiencies include subjects with pro-opiomelanocortin (POMC) deficiency, proprotein-convertase (PCSK1) deficiency, leptin receptor (LEPR) deficiency, Prader-Willi syndrome (PWS), Bardet-Biedl syndrome (BBS), Alström syndrome (AS), and selected other genetic forms of early-onset severe obesity arising from defects that impair the MC4R pathway. The gene discussed is MC4R; the disease is Prader-Willi syndrome.