ESPE Abstracts

Introduction: NR0B1 gene encodes the DAX 1 protein, an untypical member of the orphan nuclear receptor superfamily. It plays a key role in the development and function of the adrenal glands and hypothalamic-pituitary-gonadal axis. Deleterious or intragenic mutations cause X –linked congenital adrenal hypoplasia manifested as primary adrenal insufficiency (PAI) in infancy or early childhood often combined with hypogonadotropic hypogonadism.

Case report: We report the case of a male newborn with X –linked congenital adrenal hypoplasia due to a novel mutation in NR0B1 gene: c.1250del, which is a frameshift mutation that lead to development of a stop codon. The child presented at the age of three days with hypoglycemia, in the clinical setting of an early neonatal infection. Later from the age of 10 days at home he gradually developed the clinical manifestation of acute adrenal insufficiency with food intolerance, vomiting, weight loss, hypoglycemia, arterial hypotension, dehydration, hyperpigmentation and relatively uncommon sign of increased penile size. Laboratory investigations showed low blood sugar, metabolic acidosis, hyponatremia and elevated potassium with inappropriately low normal cortisol and elevated ACTH and were confirmative of mineral and glucocorticoid insufficiency. Abdominal ultrasound examination revealed a decreased size of adrenal glands. It took 14 days and two hospital admissions until diagnosis was established at clinic of pediatric endocrinology. Initial treatment was complicated by severe clinical state and small age and included intravenous glucose and saline infusion as well as parenteral glucocorticoid and oral mineralocorticoid replacement therapy. Clinical monitoring and frequent investigations were needed. Once the acute adrenal crisis was treated the patient is now on replacement doses of glucocorticoids and mineralocorticoids and oral supplements of sodium chloride. Regular monthly check ups of growth and neuropsychological development as well as level of ACTH, electrolytes, fasting blood glucose and acid base homeostasis are being done.

Conclusion: X-linked congenital adrenal hypoplasia is a rare condition. To our knowledge no other case with molecular genetic diagnosis is described in our country. If not promptly recognized and treated especially in neonatal age it may quickly deteriorate, lead to severe hypoglycemia and shock with lifelong neurologic or developmental consequences or even to a lethal outcome.