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Case Reports
. 2018 Mar 1;10(1):68-73.
doi: 10.4274/jcrpe.4638. Epub 2017 Jul 24.

A Patient with Proopiomelanocortin Deficiency: An Increasingly Important Diagnosis to Make

Semra Çetinkaya  1 , Tülay Güran  2 , Erdal Kurnaz  1 , Melikşah Keskin  1 , Elif Sağsak  1 , Senay Savaş Erdeve  1 , Jenifer P Suntharalingham  3 , Federica Buonocore  3 , John C Achermann  3 , Zehra Aycan  1   4
Affiliations
Case Reports

A Patient with Proopiomelanocortin Deficiency: An Increasingly Important Diagnosis to Make

Semra Çetinkaya et al. J Clin Res Pediatr Endocrinol. .

Abstract

Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder with early-onset obesity. Investigation of this entity have increased our insight into the important role of the leptin-melanocortin pathway in energy balance. Here, we present a patient with POMC deficiency due to a homozygous c.206delC mutation in the POMC gene. We discuss the pathogenesis of this condition with emphasis on the crosstalk between hypothalamic and peripheral signals in the development of obesity and the POMC-melanocortin 4 receptors system as a target for therapeutic intervention.

Keywords: Obesity; melanocortin 4 receptors; paediatric obesity proopiomelanocortin deficiency..

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Figures

Figure 1
Figure 1. Weight (left) and height chart (right) of the patient showing rapid weight gain after infancy (A). Chromatogram showing the homozygous c.206delC change that results in a leucine residue (CTG) being replaced by a stop codon (TGA) (upper). This mutation causes disruption of proopiomelanocortin and prevents cleavage of proopiomelanocortin into key peptides such as adrenocorticotropin hormone and α-melanocyte stimulating hormone (lower) (B) ACTH: adrenocorticotropin hormone, POMC: proopiomelanocortin, CLIP: corticotropin-like intermediate lobe peptide, γLPH: γ-lipotropin, βED: β-endorphin, MSH: melanocyte-stimulating hormone
Figure 2
Figure 2. General appearance [At appointment (red eyebrows and hair) (A), at 1.5 years old (obesity) (B), at 2.5 years old (C)]
Figure 3
Figure 3. Cartoon showing potential interactions of proopiomelanocortin neurons in appetite regulation. In the hypothalamus, nutrition and energy hemostasis is balanced by proopiomelanocortin and agouti-related peptide/neuropeptide Y through melanocortin receptors. This system is regulated by peripheral polypeptides such as leptin, ghrelin, insulin and peptide YY. In proopiomelanocortin deficiency, the appetite-stimulating effect of agouti-related peptide is not balanced by the appetite-suppressing effect of proopiomelanocortin. AgRP is co-expressed with neuropeptide Y. This peptide increases appetite and decreases energy use and metabolism. This system is mainly inhibited by leptin and stimulated by ghrelin NPY: neuropeptide Y, AgRP: agouti-related peptide, POMC: proopiomelanocortin, MSH: melanocyte-stimulating hormone, MC4R: melanocortin 4 receptors, PPY: peptide YY, GABA: gammα-amino butyric acid
See this image and copyright information in PMC

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