ESPE Abstracts

Introduction: Congenital adrenal hypoplasia, a rare cause of childhood primer adrenal insufficiency, is caused by defects in transcription factors involved in the development of adrenal gland. One of them is the NROB1 (DAX1) gene, localized in Xp21.2. DAX1 mutations have been identified that cause X-linked adrenal hypoplasia congenita. Infants affected with X-linked adrenal hypoplasia congenita may present with salt-wasting, micropenis or cryptorchidism. Moreover, delayed puberty and infertility due to hypogonadotropic hypogonadism caused by NROB1 (DAX) mutations have also been reported. We would like to present a two-months-old male diagnosed with primer adrenal insufficiency due to a nonsense mutation in NROB1 (DAX1).

Case: A two-months-old male was brought to the emergency department because of abnormal eye movements and suspicious of seizure. He was born to nonconsanguineous parents at term with a birth weight of 3400 gr. Five brother of the mother had died during neonatal period due to unidentified etiology. Physical examination was unremarkable except for mild dehydration. Genital examination revealed normal male external genitalia. His weight was 4000 gr (3-10^th centile), height was 58 cm (50-75^th centile), and blood pressure was 85/60 mmHg. Laboratory examination revealed hyponatremia (115 mmol/L), hyperkalemia (7.5 mmol/L), hyperreninemia, high ACTH (1094 pg/mL) and relatively low cortisol (8.1 µg/dl) levels. The diagnosis of primer adrenal insufficiency was established and hydrocortisone and fludrocortisone were started. Moreover, serum levels of 17-hydroxyprogesterone, DHEA-S, 11-deoxycorticosterone and 1,4-androstenedione were in normal range. The diagnosis of congenital adrenal hyperplasia (CAH) was excluded. Molecular genetic analysis of NROB1 (DAX1) revealed a hemizygos non-sense mutation [c.1282G>T (p.Glu428Ter)].

Results: Genetic defects in NROB1 (DAX1) have been reported in two thirds of male cases with undiagnosed primary adrenal insufficiency. Therefore, all male patients with non-CAH primary adrenal insufficiency should be screened for NROB1 (DAX1) defect.