A novel mutation in the MC2R gene causing familial glucocorticoid deficiency type 1

• Published in: Neonatology (Basel, Switzerland) Vol. 100; no. 3; p. 277
• Main Authors: Akin, Mustafa Ali, Akin, Leyla, Coban, Dilek, Ozturk, M Adnan, Bircan, Rifat, Kurtoglu, Selim
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2011
• Subjects: Adrenal Glands - diagnostic imaging; Adrenal Glands - pathology; Adrenal Insufficiency - drug therapy; Adrenal Insufficiency - genetics; Adrenal Insufficiency - pathology; Adrenocorticotropic Hormone - blood; Clinical Chemistry Tests; DNA Mutational Analysis; Family Health; Female; Glucocorticoids - deficiency; Glucocorticoids - genetics; Hormone Replacement Therapy; Humans; Hydrocortisone - therapeutic use; Hyperbilirubinemia - drug therapy; Hyperbilirubinemia - genetics; Hyperbilirubinemia - pathology; Hyperpigmentation - drug therapy; Hyperpigmentation - genetics; Hyperpigmentation - pathology; Hypoglycemia - drug therapy; Hypoglycemia - genetics; Hypoglycemia - pathology; Infant, Newborn; Male; Mutation; Parents; Receptor, Melanocortin, Type 2 - genetics; Steroid Metabolism, Inborn Errors - drug therapy; Steroid Metabolism, Inborn Errors - genetics; Steroid Metabolism, Inborn Errors - pathology; Ultrasonography
• ISSN: 1661-7819
• DOI: 10.1159/000323913

Familial glucocorticoid deficiency (FGD) or hereditary unresponsiveness to adrenocorticotropin (ACTH) is an autosomal recessive disorder characterized by isolated glucocorticoid deficiency associated with normal mineralocorticoid secretion. Mutations in genes encoding either ACTH receptor or melanocortin 2 receptor accessory protein are responsible for the disease in about 50% of cases, named FGD type 1 and type 2, respectively. Patients may present with hyperpigmentation, recurrent infections, failure to thrive, hypoglycemic seizures, and coma in infancy or early childhood. Here we report the case of a 17-day-old newborn diagnosed with FGD type 1 who presented with hyperbilirubinemia and hyperpigmentation, a sign which was erroneously assumed to be due to prolonged phototherapy by the referring physician. Hormone analysis showed low cortisol and high ACTH levels with normal serum electrolytes and renin-aldosterone axis. Genetic analysis revealed a novel homozygous melanocortin 2 receptor mutation p.Leu225Arg in the patient. The healthy parents were heterozygous for the mutation.