Proopiomelanocortin (POMC) deficiency is a rare genetic syndrome characterized by severe, early-onset obesity and hyperphagia, secondary adrenal insufficiency, and hypopigmentation. It is caused by homozygous or compound heterozygous loss-of-function mutations in the POMC gene, which encodes a polypeptide that is post-translationally cleaved to produce several hormones, including adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormones (MSH) (α-MSH, β-MSH, and γ-MSH), and beta-endorphin. Fewer than 50 cases of POMC deficiency have been reported in the literature. No variation in prevalence across ethnicities has been noted, and it occurs equally among both sexes.
While affected individuals are normal weight at birth, POMC deficiency manifests in infancy with rapid weight gain. MSH produced by neurons in the hypothalamus regulates energy homeostasis, including the anorexic effects of leptin, via binding to melanocortin 3 and 4 receptors. MSH deficiency leads to excessive hunger and hyperphagia, and infants with POMC deficiency typically reach weights in the 99th percentile by age 1. Hyperphagic obesity persists into adulthood in affected individuals. Congenital secondary adrenal insufficiency results from loss of adrenocorticotropic hormone (ACTH) signaling in the adrenal cortex, which can lead to hypoglycemia, cholestasis, and hyperbilirubinemia, and is potentially life-threatening if untreated.
Although pigmentation can be variable, individuals with POMC deficiency most commonly have light skin (Fitzpatrick skin phototype I) and red hair because melanin production is impaired by loss of α-MSH signaling through the melanocortin 1 receptor on melanocytes. Hypopituitarism with deficiencies of thyrotropin, growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) has rarely been reported in association with POMC deficiency.
Proopiomelanocortin deficiency
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ICD10CM:
E66.8 – Other obesity
SNOMEDCT:
702949005 – Proopiomelanocortin deficiency syndrome
E66.8 – Other obesity
SNOMEDCT:
702949005 – Proopiomelanocortin deficiency syndrome
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Last Reviewed:06/27/2017
Last Updated:06/22/2022
Last Updated:06/22/2022
Proopiomelanocortin deficiency