Background: The X-linked cytomegalic form of adrenal hypoplasia congenita (AHC), an inherited disease of the adrenal cortex, is a rare cause of adrenal insufficiency. Affected boys usually present primary adrenal insufficiency
associated with hypogonadotropic hypogonadism. The DAX1 (Dosage sensitive sex reverse Adrenal hypoplasia, chromosome X, gene 1) is located at Xp21.3 and inactivating mutations in this gene cause the X-linked
form of AHC. The great majority of DAX1 mutations described in the literature are frameshift or nonsense mutations, the missense mutations being rare.
Case report: We describe a Brazilian boy who presented adrenal insufficiency at the age of 2 years. He was successfully treated with gluco- and mineralocorticoid replacement and at the age of 16 years he was re-evaluated due to delayed puberty. Hormonal data confirmed adrenal insufficiency and hypogonadotropic hypogonadism. DNA samples from the boy and his mother were amplified by PCR with specific primers for the coding region of DAX1 gene and the PCR products were directly sequenced. Direct sequencing revealed a C>T transition at nucleotide 1133 in exon 1 of DAX1 which causes an alanina (GCC) to valine (GTC) substitution at codon
300 in the boy. Such missense mutation was not detected in his mother.
Conclusion: We conclude that a de novo missense mutation A300V in DAX1 gene, located at carboxy-terminal end of DAX1 protein, caused in the patient a severe phenotype characterized by adrenal insufficiency and hypogonadotropic hypogonadism, suggesting that this region is fundamental for DAX1 action.

Keywords: hypogonadotropic hypogonadism, adrenal insufficiency and DAX1 gene, X-linked AHC