Lin et al. (2007) described a highly consanguineous kindred from Qatar with salt-losing adrenal hypoplasia. Four of 12 children born in three nuclear families had been diagnosed with the condition. The proband (46,XY) presented at 60 days of age with pigmentation and a hypoglycemic convulsion. He had an elevated plasma renin activity (PRA), his aldosterone was inappropriately low, and he had mild hyponatremia/hyperkalemia. Thus, he was diagnosed as having adrenal hypoplasia and treated with hydrocortisone and fludrocortisone. The second child (46,XX) presented at 4 days of age with a hypoglycemic convulsion. She was hyperpigmented and found to be profoundly hypocortisolemic (<14 nmol/l), and was started on hydrocortisone alone. Given the emerging family history, two further children were diagnosed as likely affected on the first day of life on account of marked hyperpigmentation and hypoglycemia, and hydrocortisone was started almost immediately. One child was also commenced on fludrocortisone as it was believed this family had an autosomal recessive form of adrenal hypoplasia, and that treatment should be started before the onset of a salt-losing crisis. Thus, in all three cases, treatment was commenced within the first four days of life before disturbances in PRA or salt balance would likely have become manifest. At molecular level, Lin et al. (2007) identified a novel homozygous three-nucleotide deletion (579-581delTGT leading to a stop codon at 193 (Y193X)) in the MC2R gene in all affected individuals. Their parents are all carriers of this mutation and siblings are either heterozygous or normal. Lin et al. (2007) found that these affected children are likely representing the most severe end of the spectrum of familial glucocorticoid deficiency type 1 (PGD1). Lin et al. (2007) concluded that the diagnosis by MC2R mutations analysis should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis because these children may have been misdiagnosed as having salt-losing adrenal hypoplasia.

Chan et al. (2009) described a Saudi Arabian child, born to first cousin consanguineous parents, and diagnosed with FGD. The child presented with hypoglycemia, apnea, and cyanosis within the first day of his life. At three months of age, he presented with recurrent cough and shortness of breath. Five months later, he presented with collapse, bradycardia, seizures, and hypotension, which required resuscitation. Analysis revealed hypoglycemia and grossly elevated plasma ACTH levels, indicating adrenal insufficiency. He was treated with hydrocortisone replacement. However, he continued to suffer seizures and went on to develop spastic quadriplegia, visual impairment, and neurosensory deafness. Upon examination at 17 months, his height and weight were found to be between the 10th and 25th centile, while his OFC was below the 0.4th centile. He was darkly pigmented, with extremely high plasma ACTH level. He was diagnosed with FGD. Mutation analysis revealed two homozygous mutations in the MC2R genes; one of them activating, while the other was inactivating.