Familial glucocorticoid deficiency type 2: a case report

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency due to ACTH resistance.
• FGD can be caused by mutations in the ACTH receptor (MC2R) gene (FGD type 1) or the Melanocortin 2 Receptor Accessory Protein (MRAP) gene (FGD type 2).
• FGD presents in infancy or early childhood with symptoms including hypoglycemia, failure to thrive, and recurrent infections.

Observation:

• A six-month-old Turkish male infant presented with recurrent hypoglycemic convulsions.
• Laboratory results revealed low cortisol and androgen levels with high ACTH concentrations, alongside a normal mineralocorticoid axis.
• Genetic analysis excluded mutations in NR0B1 and MC2R genes.

Findings:

• A homozygous deletion (c. 106+1delG) in intron 3 of the MRAP gene was identified in the patient.
• This mutation is associated with Familial Glucocorticoid Deficiency type 2.
• This represents the first reported Turkish patient with FGD type 2 due to a known MRAP mutation.

Implications:

• This case expands the known spectrum of MRAP mutations causing FGD type 2.
• Highlights the importance of MRAP gene analysis in diagnosing FGD, particularly in diverse ethnic populations.
• Contributes to understanding the genetic basis of rare endocrine disorders and informs genetic counseling and potential therapeutic strategies.