A new DAX1 gene mutation associated with congenital adrenal hypoplasia and hypogonadotropic hypogonadism.

We report on a DAX1 gene investigation in a patient with X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) in order to identify mutations causing this disorder and to confirm the clinical diagnosis. The description of the clinical course of the condition with a detailed documentation of longitudinal data is also reported. A male newborn was referred at 45 days of life because of vomiting, dehydration, and weight loss. The diagnosis was primary adrenal insufficiency. The appropriateness of glucocorticoid therapy during the prepubertal period was difficult to judge because of elevated ACTH levels on one hand and progressive retardation of bone age on the other hand. Basal and GnRH stimulated gonadotropin levels remained low during the entire period of examination and exogenous gonadotropin treatment was begun. This had to be interrupted at age 14.6 years because of the occurrence of a 3rd degree anaplastic ependimoma of the left posterior-parietal region, without apparent lepto-meningeal involvement. The molecular analysis of DAX1 gene of the propositus showed deletion of nucleotides AAT in exon 2, resulting in the loss of the Asn430. No alterations were found in the mother and grandmother. This deleted residue lies in one of the helices forming the hydrophobic core of the ligand-binding domain (LBD); thus this mutation may be the cause of the observed phenotype. Further investigations are needed to verify its causal role in AHC associated with HH.