Glucocorticoid Deficiency 2

Alternative Names

  • GCCD2
  • Familial Glucocorticoid Deficiency 2
  • FGD2
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

607398

Mode of Inheritance

Autosomal recessive

Gene Map Locus

21q22.1

Description

Familial glucocorticoid deficiency is a rare autosomal recessive disorder characterized by unresponsiveness to adrenocorticotropic hormone (ACTH), leading to deficient secretion of cortisol and adrenal C19 androgen precursors. Mineral-corticoid production, regulated by the renin-angiotensin system, is normal. The age of presentation varies from birth to 9 years of age, with approximately half of the patients presenting in the first year of life. In the neonatal period, patients usually present with hypoglycemia and jaundice. Hyperpigmentation and/or hypoglycemia are the main symptoms in older children. Tall stature has been described in several patients. The diagnosis of familial glucocorticoid deficiency is based on clinical findings, low serum cortisol in the presence of excessively elevated ACTH, the proof of normal aldosterone production, and the exclusion of other causes of adrenal failure.

Molecular Genetics

The melanocortin 2- receptor or ACTH receptor (MC2-R or ACTH-R) with the locus at chromosome 18 p 11.2 is the shortest G- protein - coupled receptor to date. After the first description of familial glucocorticoid deficiency associated with point mutation in the ACTH receptor, several other types of mutations have been described with poor correlation between phenotype and genotype. However, in more than half of the patients with familial glucocorticoid deficiency, no mutation can be identified within the coding region of the MC2-R. That is why familial glucocorticoid deficiency can be divided into type 1 and type 2, with and without MC2-R mutations, respectively. The molecular background of familial glucocorticoid deficiency type 2 is not yet apparent. A genome-wide search is in progress to clarify whether familial glucocorticoid deficiency type 2 comprises a heterogeneous group of diseases with different etiologies such as mutations in signaling molecules, MC2-R transcription factors/translational regulators, or

factors involved in the differentiation of adrenocortical cells.

 

Epidemiology in the Arab World

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Other Reports

Yemen

Ramachandran et al. (2003) described two related patients with familial glucocorticoid deficiency type 2 from an extended family of Yemeni origin. The first patient was a hypoglycemis male neonate. In view of the hyperpigmentation, hypoglycemia, hypotonia, and lethargy, the possibility of adrenal insufficiency was considered. Hydrocortisone replacement therapy was started on day 10. The second patient  was a full-term male baby born to consanguineous parents. He had asymptomatic hypoglycemia with blood glucose <10 mg/dl. Glucocorticoids were found to be deficient. Replacement therapy with hydrocortisone was started on the fourth day of life. No mutations, deletions, or addition abnormalities were detected within or outside the coding sequence of the MC2-R gene. 

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