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

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Isolated hypocortisolism from ACTH deficiency can stem from proopiomelanocortin (POMC) gene mutations.
• Loss-of-function POMC mutations typically manifest as adrenal insufficiency, obesity, and red hair.

Purpose of the Study:

• To report a case of congenital adrenal insufficiency with a novel POMC mutation and atypical clinical presentation.
• To emphasize the importance of considering POMC mutations in early-onset obesity and adrenal insufficiency, even without characteristic pigmentary changes.

Main Methods:

• Clinical case presentation of an 18-month-old Hispanic female.
• Endocrine evaluation for hypoglycemia and ACTH deficiency.
• POMC gene sequencing to identify the genetic mutation.

Main Results:

• The patient presented with hypoglycemia and ACTH deficiency at 9 months old.
• A novel homozygous c.231C > A POMC mutation, predicted to cause a premature termination codon, was identified.
• The patient exhibited obesity and hypocortisolism but lacked the typical red hair phenotype.

Conclusions:

• This case demonstrates a novel POMC mutation leading to hypocortisolism and severe obesity.
• The absence of red hair in this patient underscores that POMC mutations can present with atypical phenotypes.
• POMC gene analysis should be considered in infants with severe early-onset obesity and adrenal insufficiency, irrespective of pigmentation.