Primary Adrenal Insufficiency Caused by a Novel Mutation in DAX1 Gene

In tro duc ti on Primary adrenal insufficiency can be caused by a deficiency in steroid biosynthesis or an abnormal adrenal gland development. Adrenal hypoplasia congenita (AHC) is an inherited disorder of adrenal development resulting in primary adrenal insufficiency (1). It has an estimated frequency of 1:12 500 live births (2) and can be inherited as an autosomal recessive or an X-linked disease (3). X-linked AHC is caused by deletions or mutations in DAX1 gene (dosage-sensitive sex reversal, AHC critical region on the X chromosome, gene 1; NROB1) situated in Xp21 (4). The DAX1 gene consists of two exons of 1168 and 245 bp, respectively, and encodes a 470 amino acid protein which belongs to the nuclear hormone receptor superfamily (5). DAX1 is expressed in the adrenal cortex, in the pituitary, in the hypothalamic ventral nucleus, in Sertoli and Leydig cells in the testis, and in theca and granulosa cells in the ovary (3,5,6). X-linked AHC has variable clinical presentations (7,8,9). Boys with DAX1 mutations typically present with primary adrenal failure. In these patients, the adrenal gland fails to develop fully. Histologically, the adrenal cortex permanent zone is absent, and there are residual cytomegalic cells (10). Urgent mineralocorticoid and glucocorticoid replacement is mandatory (11). Most boys fail to enter puberty and must be given testosterone replacement therapy in adulthood. Here, we report a male newborn with AHC who presented with adrenal insufficiency due to a novel mutation in the DAX1 gene