FAMILIAL GLUCOCORTICOID DEFICIENCY

MC2R, MRAP, STAR, MCM4 AND NNT GENE ANALYSIS

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency.  Patients typically present with symptoms related to their low cortisol and high ACTH. Glucocorticoid deficiency may lead to hypoglycemic seizures and/or failure to thrive within the neonatal period or very early childhood, while older children may present with recurrent infections. The condition is potentially fatal if left untreated and in the long term recurrent hypoglycaemia can lead to learning difficulties in addition to other neurological sequelae. Excessive plasma ACTH often results in hyperpigmentation due to overstimulation of melanocortin 1 receptors (MC1R). This hyperpigmentation can be present from birth or may develop over time.

Disease-causing variants in MC2R, MRAP, STAR, MCM4 and NNT account for approximately 60% of all cases of FGD (Eirini et al 2013, Molecular and Cellular Endocrinology 371:195-200).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.