Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

(*) mandatory field


Other search option(s)

Obesity due to pro-opiomelanocortin deficiency

Synonym(s) POMC deficiency
Prevalence <1 / 1 000 000
Inheritance Autosomal recessive
Age of onset Infancy
  • E66.8
MeSH -
MedDRA -


Disease definition

Pro-opiomelanocortin (POMC) deficiency is a form of monogenic obesity resulting in severe early-onset obesity, adrenal insufficiency, red hair and pale skin.


It is has been described in less than 10 patients.

Clinical description

Patients with POMC deficiency usually present in the neonatal period with hypoglycaemic seizures, hyperbilirubinaemia and cholestasis to due to secondary congenital hypocortisolism. Hyperphagia is noted from the first weeks of life leading to severe obesity before one year of age. Subclinical hypothyroidism was also reported.


Complete POMC deficiency is caused by homozygous or compound heterozygous loss-of-function mutations in the POMC gene (chromosome 2p23.3). POMC is regulated by leptin and is cleaved by prohormone convertases to produce the melanocortin receptor (MC-R) ligands adrenocorticotrophin (ACTH) and melanocyte-stimulating hormones (MSH) alpha, beta and gamma. The red hair pigmentation, adrenal insufficiency and obesity are caused by deficiencies in the ligands and subsequent lack of activation of the MC1, MC2, and MC4 receptors, respectively. In addition to complete POMC deficiency, a few individuals with isolated deficiency of the MC4-R POMC-derived ligand, beta-MSH, have also been described. These individuals carry a distinct POMC mutation in the region encoding beta-MSH. This isolated deficiency of beta-MSH leads to a clinical phenotype similar to that observed in MC4-R deficiency (childhood obesity, hyperphagia and increased linear growth) but is not associated with red hair or adrenal insufficiency.

Diagnostic methods

Diagnosis of complete POMC deficiency may be suspected on the basis of the clinical manifestations of the disease and can be confirmed by identification of mutations in the POMC gene. Analysis of the serum reveals an absence of pituitary-derived POMC peptides, even after stimulation.

Differential diagnosis

Differential diagnosis includes combined pituitary hormone deficiencies, which can be excludedby multiple pituitary hormone stimulation tests.

Genetic counseling

Complete POMC deficiency is transmitted as an autosomal recessive trait.

Management and treatment

At present, there is no specific treatment. The neonatal complications of POMC deficiency may lead to lethal hepatic failure if left untreated, with patients requiring prompt and long-term hydrocortisone substitution therapy. Advances in melanocortin peptide therapy may lead to the development of MC4R agonists capable of improving melanocortin function in these patients. However, an initial 3-month trail with intranasal administration the ACTH 4-10 melancortin fragment did not lead to a reduction in body weight. Administration of thyroid hormone was also found to have no effect on the obesity.


Although the specific prognosis for this disease has not yet been defined, it is likely these patients are at increased risk of complications (cardiovascular disease, cancer and type 2 diabetes) present in other obese patients.

Expert reviewer(s)

  • Pr Sebastiano FILETTI

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.

Captcha image

Detailed information

Clinical genetics review
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.