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

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.

Kaynakça

Biebermann H, Kühnen P, Kleinau G, Krude H. The neuroendocrine circuitry controlled by POMC, MSH, and AGRP. Handb Exp Pharmacol 2012;209:47-75.

Krude H, Grüters A. Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome. Trends Endocrinol Metab 2000;11:15-22.

Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998;19:155-157.

Challis BG, Millington GWM.Gene Reviews. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, DolanCR, Fong CT, Smith RJH, Stephens K, editors. Proopiomelanocortin Deficiency. GeneReviews® [Internet]. Seattle WA: University of Washington, Seattle; 1993-2015. 2013 Dec 12.

Guran T, Buonocore F, Saka N, Ozbek MN, Aycan Z, Bereket A, Bas F, Darcan S, Bideci A, Guven A, Demir K, Akinci A, Buyukinan M, Aydin BK, Turan S, Agladioglu SY, Atay Z, Abali ZY, Tarim O, Catli G, Yuksel B, Akcay T, Yildiz M, Ozen S, Doger E, Demirbilek H, Ucar A, Isik E, Ozhan B, Bolu S, Ozgen IT, Suntharalingham JP, Achermann JC. Rare causes of primary adrenal insufficiency: Genetic and clinical characterization of a large nationwide cohort. J Clin Endocrinol Metab 2016;101:284-292.

Mendiratta MS, Yang Y, Balazs AE, Willis AS, Eng CM, Karaviti LP, Potocki L. Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation. Int J Pediatr Endocrinol 2011;1:1-6.

Farooqi IS, Drop S, ClementsA, Keogh JM, Biernacka J, Lowenbein S, Challis BG, O’Rahilly S. Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes 2006;55:2549-2553.

Clément K, Dubern B, Mencarelli M, Czernichow P, Ito S, Wakamatsu K, Barsh GS, Vaisse C, Leger J. Unexpected endocrine features and normal pigmentation in a young adult patient carrying a novel homozygous mutation in the POMC gene. J Clin Endocrinol Metab 2008;93:4955-4962.

Cirillo G, Marini R, Ito S, Wakamatsu K, Scianguetta S, Bizzarri C, Romano A, Grandone A, Perrone L, Cappa M, Miraglia Del Giudice E. Lack of red hair phenotype in a North-African obese child homozygous for a novel POMC null mutation: non sense-mediated decay RNA evaluation and hair pigment chemical analysis. Br J Dermatol 2012;167:1393-1395.

Krude H, Biebermann H, Schnabel D, Tansek MZ, Theunissen P, Mullis PE, Grüters A. Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10. J Clin Endocrinol Metab 2003;88:4633-4640.

Kim MS, Small CJ, Stanley SA, Morgan DG, Seal LJ, Kong WM, Edwards CM, Abusnana S, Sunter D, Ghatei MA, Bloom SR. The central melanocortin system affects the hypothalamo-pituitarythyroid axis and may mediate the effect of leptin. J Clin Invest 2000;105:1005-1011.

Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjøorbaek C, Elmquist JK, Flier JS, Hollenberg AN. Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. J ClinInvest 2001;107:111-120.

Amin A, Dhillo WS, Murphy KG. The central effects of thyroid hormones on appetite. J Thyroid Res 2011;2011:306510.

Darcan S, Can S, Goksen D, Asar G. Transient salt wasting in POMCdeficiency due to infection induced stress. Exp Clin Endocrinol Diabetes 2010;118:281-283.

Özen S, Özcan N, Uçar SK, Gökşen D, Darcan Ş. Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency. J Pediatr Endocrinol Metab 2015;28:691-694.

Samuels ME, Gallo-Payet N, Pinard S, Hasselmann C, Magne F, Patry L, Chouinard L, Schwartzentruber J, René P, Sawyer N, Bouvier M, Djemli A, Delvin E, Huot C, Eugene D, Deal CL, Van Vliet G, Majewski J, Deladoëy J; FORGE Canada Consortium. Bioinactive ACTH causing glucocorticoid deficiency. J Clin Endocrinol Metab 2013;98:736-742.

Challis BG, Pritchard LE, Creemers JW, Delplanque J, Keogh JM, Luan J, Wareham NJ, Yeo GS, Bhattacharyya S, Froguel P, White A, Farooqi IS, O’Rahilly S. A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum Mol Genet 2002;11:1997-2004.

Buono P, Pasanisi F, Nardelli C, Ieno L, Capone S, Liguori R, Finelli C, Oriani G, Contaldo F, Sacchetti L. Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy. Clin Chem 2005;51:1358-1364.

Shabana, Hasnain S. Prevalence of POMC R236G mutation in Pakistan. Obes Res Clin Pract 2015.

Ozen S, Aldemir O. Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency. Genet Couns 2012;23:493-495.

Hung CN, Poon WT, Lee CY, Law CY, Chan AY. A case of early-onset obesity, hypocortisolism, and skin pigmentation problem due to a novel homozygous mutation in the proopiomelanocortin (POMC) gene in an Indian boy. J Pediatr Endocrinol Metab 2012;25:175-179.

Kaynak Göster

417 141

Arşiv
Sayıdaki Diğer Makaleler

Serum Nesfatin-1 Levels in Girls with Idiopathic Central Precocious Puberty

Ayça ALTINCIK, OYA SAYIN

Metachronous Synovial Sarcoma After Treatment of Mixed Germ Cell Tumor in a Child with Complete Gonadal Dysgenesis

Feryal KARAHAN, ELVAN ÇAĞLAR ÇITAK, Emel YAMAN, Mehmet ALAKAYA, Fatih SAĞCAN, Eda Bengi YILMAZ, Funda KUŞ, İCLAL GÜRSES, YÜKSEL BALCI

Effect of Intrahepatic Cholestasis of Pregnancy on Neonatal Birth Weight: A Meta-Analysis

Li Lİ, Yuan-Hua CHEN, Yuan-Yuan YANG, Lin CONG

The Evaluation of Cases with Y-Chromosome Gonadal Dysgenesis: Clinical Experience over 18 Years

MERİH BERBEROĞLU, ZEYNEP ŞIKLAR

The Relationship Between Blood Pressure and Sleep Duration in Turkish Children: A Cross-Sectional Study

CENGİZ BAL, AHMET ÖZTÜRK, BETÜL ÇİÇEK, Ahmet ÖZDEMİR, Gökmen ZARARSIZ, DEMET ÜNALAN, Gözde Ertürk ZARARSIZ, SELÇUK KORKMAZ, DİNÇER GÖKSÜLÜK, Vahap ELDEM, Sevda İSMAİLOĞULLARI, EMİNE ERDEM, Mümtaz M. MAZICIOĞLU, Selim KURTOĞLU

A Meta-Analysis and an Evaluation of Trends in Obesity Prevalence among Children and Adolescents in Turkey: 1990 through 2015

ZÜLEYHA ALPER, İLKER ERCAN, YEŞİM UNCU

An Assessment of Retinal Nerve Fiber Layer Thickness in Non-Diabetic Obese Children and Adolescents

Bediz ÖZEN, Hakan ÖZTÜRK, GÖNÜL ÇATLI, BUMİN NURİ DÜNDAR

Letter to the Editor Regarding “Assessment of Retinal Nerve Fiber Layer Thickness in Non-Diabetic Obese Children and Adolescents”

ÖMER KARTI

Could Alerting Physicians for Low Alkaline Phosphatase Levels Be Helpful in Early Diagnosis of Hypophosphatasia?

Asma DEEB, Abubaker ELFATİH

Vitamin D Deficiency in Pregnant Women and Their Infants

ABDURRAHMAN AVAR ÖZDEMİR, Yasemin ERCAN GÜNDEMİR, Mustafa KÜÇÜKAYDIN, Deniz YILDIRAN SARICI, Yusuf ELGÖRMÜŞ, YAKUP ÇAĞ, GÜNAL BİLEK