Abstract
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder in which the adrenal cortex fails to respond appropriately to stimulation by adrenocorticotropic hormone (ACTH) to produce cortisol. The disease is characterized in laboratory testing by glucocorticoid deficiency and markedly elevated ACTH levels. FGD may present in infancy or early childhood with symptoms related to low cortisol and high ACTH, such as hyperpigmentation, severe hypoglycemia, failure to thrive and recurrent infections. Mutations in the MC2R accessory protein (MRAP) cause FGD types 2, which accounts for approximately 15-20% of FGD cases. Here, we report a female neonate of Chinese Han origin, who presented with noted hyperpigmentation at birth. Laboratory investigations revealed hypocortisolaemia (cortisol < 1.0 μg/dl) and elevated plasma ACTH (1051 pg/ml). She responded to hydrocortisone treatment. Genetic studies confirmed the diagnosis showing homozygous deletion (c. 106 + 1delG) in intron 3 of MRAP gene, a mutation already reported as responsible for FDG type 2. This mutation can cause complete lack of ACTH response thus explaining the early presentation in this case. Her parents and maternal grandmother were heterozygous for the same mutation. To our knowledge, this is the first Chinese Han patient reported with FGD type 2 due to a known MRAP mutation.