Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation

Meenal S Mendiratta,Alecia S Willis,Christine M Eng,Lefkothea P Karaviti,Lorraine Potocki,Andrea E Balazs,Yaping Yang

doi:10.1186/1687-9856-2011-5

Abstract

Isolated hypocortisolism due to ACTH deficiency is a rare condition that can be caused by homozygous or compound heterozygous mutations in the gene encoding proopiomelanocortin (POMC). Loss of function mutations of POMC gene typically results in adrenal insufficiency, obesity and red hair. We describe an 18 month old Hispanic female with congenital adrenal insufficiency, a novel POMC mutation and atypical clinical features. The patient presented at the age of 9 months with hypoglycemia and the endocrine evaluation resulted in a diagnosis of ACTH deficiency. She developed extreme weight gain prompting sequence analysis of POMC, which revealed a homozygous c.231C > A change which is predicted to result in a premature termination codon. The case we report had obesity, hypocortisolism but lacked red hair which is typical for subjects with POMC mutations. Mutations of POMC should be considered in individuals with severe early onset obesity and adrenal insufficiency even when they lack the typical pigmentary phenotype.

Highlights

Congenital isolated adrenocorticotropic hormone (ACTH) deficiency is a rare condition
Congenital isolated ACTH deficiency is a rare condition. It is characterized by decreased plasma adrenocorticotropic hormone (ACTH) concentration resulting in adrenal insufficiency and low serum cortisol concentration and lack of hyperpigmentation
We describe an individual with early onset obesity, adrenal insufficiency and a novel POMC mutation but without the typical pigmentary phenotype of red hair and pale skin

Summary

Introduction

Congenital isolated ACTH deficiency is a rare condition It is characterized by decreased plasma adrenocorticotropic hormone (ACTH) concentration resulting in adrenal insufficiency and low serum cortisol concentration and lack of hyperpigmentation. These subjects show no ACTH response to exogenous corticotrophin releasing hormone (CRH) administration and have a normal pituitary morphology. Case Report A 9 month old female presented with hypoglycemia and hyponatremia following a three day history of fever, emesis, poor oral intake and progressive lethargy She was the first born child of nonconsanguinous parents of Hispanic ethnicity whose family history was noncontributory. Congenital isolated ACTH deficiency was diagnosed based on her clinical presentation, absent hyperpigmentation, low basal and stimulated cortisol levels and normal levels of other pituitary hormones.

Discussion

Findings

18. Rees JL