Abstract
A male newborn was investigated at 3 weeks of age for failure to thrive with no other symptoms. Hyponatraemia 116 mmol/I and hyperkalaemia 6,8 mmol/I were found.
For strong suspicion of congenital adrenal hyperplasia, treatment with Hydrocortisone and Fludrocortisone was started. A consequent investigation following a short period off therapy proved high ACTH levels but low 17-hydroxyprogesteron and cortisol before and after ACTH stimulation.
The urinary output of aldosterone level was also decreased. The boy had retractile testicles.
On substitution therapy, he did well but his growth was partly retarded. The findings were suggestive for adrenal hypoplasia congenita (AHC) - a serious form of adrenal failure which is usually lethal without treatment.
The X-linked form of AHC is caused by mutations of the DAX-1 gene. Our patient had a missense mutation L278R which is one of the two first DAX-1 gene defect ever found in Czech patients.
DAX-1 encodes for an unusual member of nuclear receptor superfamily which acts as a transcriptional. It is expressed in urogenital ridge, adrenals, gonads, ventromedial hypothalamus and pituitary gonadotrophs.
Males with DAX-1 gene defect suffer not only from AHC but also from hypogonadotropic hypogonadism and primary spermatogenesis defect.