Pro-opiomelanocortin Deficiency

Heiko Krude and Annette Grüters

in Genetics of Obesity Syndromes

Published on behalf of Oxford University Press

Published in print July 2009 | ISBN: 9780195300161
Published online October 2012 | e-ISBN: 9780199975198 | DOI:

Series: Oxford Monographs on Medical Genetics

Pro-opiomelanocortin Deficiency

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  • Clinical Genetics
  • Endocrinology and Diabetes


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Fifty years after the discovery of MSH and 20 years after the initial cloning of the POMC gene, one of the key roles of MSH in human physiology was described, e.g., hypothalamic regulation of body weight. Due to its diverse function, the POMC gene defect results in a complex clinical disease which is highlighted by the triad of isolated corticotropin deficiency, severe early-onset obesity, and hypopigmentation. So far all patients with complete loss-of-function mutations of the POMC gene have been affected with obesity and hypocortisolism, while red hair pigmentation has varied according to the ethnic background. Mutations in POMC are extremely rare in nonsyndromic common obesity (〈0.1%). Therefore, further genetic diagnostic workup of patients with obesity needs to be focused and investigation of the POMC gene seems to be reasonable only in those few patients with associated secondary hypocortisolism.

A molecular diagnosis–based treatment of obesity in POMC deficiency seems to be achievable in terms of MSH-based MC4R ligands. In rodents, intraperitoneal administration of MSH has been reported to result in significant weight reduction in pomc null mice. Although the situation of concomitant Cortisol deficiency and the small number of treated animals raises some concern about the validity of these MSH treatment results in mice, it is plausible that MSH-based substitution in POMC-deficient patients represents an option for a tailored treatment of severe obesity in POMC deficiency. However, administration of MSH-derived, MC4R-selective agonists either subcutaneously or intranasally results in immediate stimulation of penile erections within 30 min in male probands (King et al. 2007). While these effects are the basis for a new unexpected treatment option for erectile dysfunction, they obviously interfere with the use of these substances as antiobesity drug, and especially treatment of POMC-deficient children was hampered by these effects on sexual behavior. Other potential therapies for POMC deficiency are yet to emerge, although the development of β-MSH analogues holds promise for the future.

Chapter.  5523 words.  Illustrated.

Subjects: Clinical Genetics ; Endocrinology and Diabetes

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