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.
[See : Yemen > Ramachandran et al., 2003].
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 male baby who had two normal siblings. Two of the father's siblings, a girl and a boy, died in the neonatal period from unknown causes. The baby had Apgar scores of 8 and 9 at 1 and 5 minutes after birth. The blood glucose was <10 mg/dl and needed 8mg/kg per minute of glucose to maintain normoglycemia. Over the ensuing hours, he became lethargic; hypotonia worsened, and he had poor sucking reflex. In view of the hyperpigmentation, hypoglycemia, hypotonia, and lethargy, the possibility of adrenal insufficiency was considered. Hydrocortisone replacement therapy was started on day 10. Over the subsequent few weeks, the body pigmentation decreased and there was adequate weight gain. The second patient that Ramachandran et al. (2003) described 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. Ramachandran et al. (2003) performed DNA analysis on both patients to detect any mutations of the adrenocorticotropic hormone (ACTH) receptor. No mutations, deletions, or addition abnormalities were detected in the coding sequence of the MC2-R gene. Ramachandran et al. (2003) conducted a linkage analysis and excluded the possibility of mutations present outside the coding sequence of the MC2-R gene.