Obesity and Hyperphagia With Increased Defective ACTH: A Novel POMC Variant.
J Clin Endocrinol Metab
; 107(9): e3699-e3704, 2022 08 18.
Article
en En
| MEDLINE
| ID: mdl-35737586
ABSTRACT
OBJECTIVE:
Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin-stimulating hormone (α-MSH) and desacetyl-α-melanocortin-stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance.METHODS:
We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant.RESULTS:
The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism.CONCLUSION:
The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proopiomelanocortina
/
Hormona Adrenocorticotrópica
Límite:
Humans
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2022
Tipo del documento:
Article
País de afiliación:
Países Bajos