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

Çeti̇nkaya, Semra; Güran, Tülay; Kurnaz, Erdal; Keskin, Mahmut; Sağsak, Elif; Erdeve, Şenay Savaş; Suntharalingham, Jenifer P.; Buonocore, Federica; Achermann, John C.; Aycan, Zehra

doi:10.4274/jcrpe.4638

Cited by 20 publications

(16 citation statements)

References 19 publications

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“…Another girl was reported to have spontaneous earlier normal puberty with late normal timing of menarche ( 17 ), indicating slower progressing puberty; however, one of the POMC gene variants in this girl targeted only ACTH and α -MSH and not the other POMC-derived peptides. Low gonadotropins during anticipated mini-puberty were observed in a 2.5-month-old girl, indicating congenital hypogonadotropic hypogonadism ( 23 ). The data suggest the follow-up for possible hypogonadism in girls with POMC deficiency as reasonable.…”

Section: Discussionmentioning

confidence: 92%

“…Actually, in most dark-haired patients, even γ -MSH synthesis is abolished ( 9 , 10 , 13 , 15 , 22 ); dark hair color phenotype in these patients, therefore, seems not to result from any residual POMC-derived melanocortin. Furthermore, there are few other reports of patients displaying different phenotypes with either red or brown hair while having the same genotype ( 7 , 10 , 16 , 23 ). The common denominator of patients with darker pigmentations seems to be a non-Caucasian ethnic origin, including our female patient that is of Romani descent.…”

Section: Discussionmentioning

confidence: 99%

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Two Cases With an Early Presented Proopiomelanocortin Deficiency—A Long-Term Follow-Up and Systematic Literature Review

et al. 2021

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Proopiomelanocortin (POMC) deficiency is an extremely rare inherited autosomal recessive disorder characterized by severe obesity, adrenal insufficiency, skin hypopigmentation, and red hair. It is caused by pathogenic variants in the POMC gene that codes the proopiomelanocortin polypeptide which is cleaved to several peptides; the most notable ones are adrenocorticotropic hormone (ACTH), alpha- and beta-melanocyte-stimulating hormones (α-MSH and β-MSH); the latter two are crucial in melanogenesis and the energy balance by regulating feeding behavior and energy homeostasis through melanocortin receptor 4 (MC4R). The lack of its regulation leads to polyphagia and early onset severe obesity. A novel MC4R agonist, setmelanotide, has shown promising results regarding weight loss in patients with POMC deficiency. A systematic review on previously published clinical and genetic characteristics of patients with POMC deficiency and additional data obtained from two unrelated patients in our care was performed. A 25-year-old male patient, partly previously reported, was remarkable for childhood developed type 1 diabetes (T1D), transient growth hormone deficiency, and delayed puberty. The second case is a girl with an unusual presentation with central hypothyroidism and normal pigmentation of skin and hair. Of all evaluated cases, only 50% of patients had characteristic red hair, fair skin, and eye phenotype. Central hypothyroidism was reported in 36% of patients; furthermore, scarce adolescent data indicate possible growth axis dysbalance and central hypogonadism. T1D was unexpectedly prevalent in POMC deficiency, reported in 14% of patients, which could be an underestimation. POMC deficiency reveals to be a syndrome with several endocrinological abnormalities, some of which may become apparent with time. Apart from timely diagnosis, careful clinical follow-up of patients through childhood and adolescence for possible additional disease manifestations is warranted.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Two Cases With an Early Presented Proopiomelanocortin Deficiency—A Long-Term Follow-Up and Systematic Literature Review

et al. 2021

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“…POMC is synthesised by the corticotropic cells of the pituitary gland. POMC is then cleaved to form α‐, β‐, γ‐MSH, ACTH, β‐, γ‐lipotrophin and endorphins, stimulated by corticotropin‐releasing hormone 7 . α‐MSH acts via the Melanocortin (MC) 1 receptor to produce skin pigmentation, and both α‐ and β‐MSH act via the MC4 receptor to influence appetite.…”

Section: Discussion and Review Of The Literaturementioning

confidence: 99%

“…Proopiomelanocortin (POMC) is synthesised in the pituitary corticotropes and cleaved to produce melanocyte‐stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), β‐, and γ‐lipotropin and endorphins. Congenital POMC deficiency was first reported in 1998 1 and is characterised by early onset obesity, central adrenal insufficiency, 2 red hair and pale skin 1–7 . The condition appears to be extremely rare with fewer than 50 affected individuals reported 2,7 .…”

Section: Patientmentioning

confidence: 99%

Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases

Graves

Khouri

Kristidis

et al. 2021

J Paediatrics Child Health

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Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder characterised by adrenocorticotropic hormone (ACTH) deficiency, red hair and hyperphagic obesity. Two unrelated cases presented with hypoglycaemia due to isolated ACTH deficiency in the neonatal period. POMC deficiency was suspected at age 2 years (c.133‐2A>C) and at age 9 months (c.64del) due to infantile hyperphagic obesity. Neither patient had a convincing red hair phenotype at the time of diagnostic suspicion, illustrating the importance of suspecting POMC deficiency in isolated ACTH deficiency. Both patients have normal psychomotor development, whereas the only other reported case of c.64del had significant delay. This suggests, if ACTH deficiency is treated early in the neonatal period, that psychomotor retardation is not a part of the phenotype. We review 24 reported cases of POMC deficiency published to date. Although there is no current specific treatment for obesity in POMC deficiency, we anticipate that setmelanotide may be a useful future treatment option.

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“…Defects in POMC itself also result in ACTH insufficiency and adrenal dysfunction in early infancy ( 14 ). Children have red (or auburn) hair and pale skin due to MSH deficiency, and profound hyperphagia and weight gain from later infancy due to hypothalamic POMC disruption ( 15 ). MC4R agonists, which mimic MSH, have had promising results in suppressing hyperphagia in this condition, so it is an important diagnosis to make ( 16 ).…”

Section: Secondary Adrenal Insufficiencymentioning

confidence: 99%

Current Insights Into Adrenal Insufficiency in the Newborn and Young Infant

et al. 2020

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Adrenal insufficiency (AI) is a potentially life-threatening condition that can be difficult to diagnose, especially if it is not considered as a potential cause of a child's clinical presentation or unexpected deterioration. Children who present with AI in early life can have signs of glucocorticoid deficiency (hyperpigmentation, hypoglycemia, prolonged jaundice, poor weight gain), mineralocorticoid deficiency (hypotension, salt loss, collapse), adrenal androgen excess (atypical genitalia), or associated features linked to a specific underlying condition. Here, we provide an overview of causes of childhood AI, with a focus on genetic conditions that present in the first few months of life. Reaching a specific diagnosis can have lifelong implications for focusing management in an individual, and for counseling the family about inheritance and the risk of recurrence.

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

Cited by 20 publications

References 19 publications

Two Cases With an Early Presented Proopiomelanocortin Deficiency—A Long-Term Follow-Up and Systematic Literature Review

Two Cases With an Early Presented Proopiomelanocortin Deficiency—A Long-Term Follow-Up and Systematic Literature Review

Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases

Current Insights Into Adrenal Insufficiency in the Newborn and Young Infant

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