Familial Glucocorticoid Deficiency Type 1: A Case Report

Introduction: Familial glucocorticoid deficiency (FGD) is a rare genetic disorder with an autosomal recessive pattern and belongs to ACTH sensivity disorders.ACTH is necessary for the normal secretion of adrenal androgen.. FGD has two main types caused by mutations in Melanocortin 2 receptor (MC2R) and melanocortin-2 receptor associated protein (MRAP) genes. Mutations in MC2R lead to both low cortisol level in serum and high adrenocorticotropic hormone (ACTH) level. MRAP encodes a protein which plays an important role in trafficking MC2R to the cell surface. The main clinical phenotypes of this disease in diagnosed patients include hypoglycemia, recurrent convulsions, or circulatory collapse. Patients with FGD often have undetectable level of adrenal. These findings indicate the importance of ACTH, MC2R and MRAP. Here we report an Iranian girl with FGD investigated for mutations in these two genesMaterials & Methods: A 2-year-old Iranian girl born to consanguineous parents. Genetic analysis and direct sequencing was performed in order to find any alterations Results: Our genetic analysis revealed a Homozygote missense mutation in exon2 MC2R (p.Ile84Asn) c.251T> A and no mutations were found in MRAP gene. Our Insilico analysis in Mutation Taster predicted this mutation as a disease causing variant.Conclusion & discussion: The diagnosis of FGD is based on both the clinical phenotypes and biochemical findings such as ACTH level.Adrenal level alone is not enough for the detection of FGD as some affected patients have normal adrenal level.This indicate the combination of Genetic test and Blood analysis together. The discovery of new mutations in FGD enable us to identify FGD affected patients. In addition, genetic diagnostic tests help us to recognize patients who have unknown adrenal failure

Keywords:

Familial glucocorticoid deficiency , Genetics , , melanocortin 2 receptor (MC2R) , melanocortin-2 receptor associated protein (MRAP)