{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:29:14Z","timestamp":1792466954147,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Proopiomelanocortin (POMC) deficiency is an extremely rare inherited autosomal recessive disorder characterized by severe obesity, adrenal insufficiency, skin hypopigmentation, and red hair. It is caused by pathogenic variants in the <jats:italic>POMC<\/jats:italic> gene that codes the proopiomelanocortin polypeptide which is cleaved to several peptides; the most notable ones are adrenocorticotropic hormone (ACTH), alpha- and beta-melanocyte-stimulating hormones (<jats:italic>\u03b1<\/jats:italic>-MSH and <jats:italic>\u03b2<\/jats:italic>-MSH); the latter two are crucial in melanogenesis and the energy balance by regulating feeding behavior and energy homeostasis through melanocortin receptor 4 (MC4R). The lack of its regulation leads to polyphagia and early onset severe obesity. A novel MC4R agonist, setmelanotide, has shown promising results regarding weight loss in patients with POMC deficiency. A systematic review on previously published clinical and genetic characteristics of patients with POMC deficiency and additional data obtained from two unrelated patients in our care was performed. A 25-year-old male patient, partly previously reported, was remarkable for childhood developed type 1 diabetes (T1D), transient growth hormone deficiency, and delayed puberty. The second case is a girl with an unusual presentation with central hypothyroidism and normal pigmentation of skin and hair. Of all evaluated cases, only 50% of patients had characteristic red hair, fair skin, and eye phenotype. Central hypothyroidism was reported in 36% of patients; furthermore, scarce adolescent data indicate possible growth axis dysbalance and central hypogonadism. T1D was unexpectedly prevalent in POMC deficiency, reported in 14% of patients, which could be an underestimation. POMC deficiency reveals to be a syndrome with several endocrinological abnormalities, some of which may become apparent with time. Apart from timely diagnosis, careful clinical follow-up of patients through childhood and adolescence for possible additional disease manifestations is warranted.<\/jats:p>","DOI":"10.3389\/fendo.2021.689387","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T09:33:32Z","timestamp":1623231212000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Two Cases With an Early Presented Proopiomelanocortin Deficiency\u2014A Long-Term Follow-Up and Systematic Literature Review"],"prefix":"10.3389","volume":"12","author":[{"given":"Nadan","family":"Gregoric","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urh","family":"Groselj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasa","family":"Bratina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marusa","family":"Debeljak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojca","family":"Zerjav Tansek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasna","family":"Suput Omladic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jernej","family":"Kovac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadej","family":"Battelino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Primoz","family":"Kotnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Avbelj Stefanija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/978-3-642-24716-3_3","article-title":"The Neuroendocrine Circuitry Controlled by POMC, MSH, and AGRP","volume":"209","author":"Biebermann","year":"2012","journal-title":"Handb Exp Pharmacol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/s42255-021-00345-3","article-title":"POMC Neuronal Heterogeneity in Energy Balance and Beyond: An Integrated View","volume":"3","author":"Quarta","year":"2021","journal-title":"Nat Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30364-8","article-title":"Setmelanotide POMC and LEPR Phase 3 Trial Investigators. 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