Adrenal hypoplasia congenita and hypogonadotropic hypogonadism: Studies inthree generations

Two brothers presenting with vomiting and dehydration in the neonatal perio d, recovered with rehydration only to develop overt adrenal insufficiency l ater in childhood, With steroid replacement therapy they enjoyed good healt h, but failed to enter puberty because of gonadotropin deficiency, A nephew , the older son of their sister, presented in a similar fashion 25 years la ter with adrenal insufficiency confirmed at age 2 years. Like his uncles, t he nephew was thought to have adrenal hypoplasia, but the presence or absen ce of hypogonadotropic hypogonadism could not be ascertained. The observati on recently that mutations in the dosage-sensitive sex reversal adrenal hyp oplasia congenita critical region on the X-chromosome gene 1 (DAX-1) may be responsible for both adrenal hypoplasia con genita and hypogonadotropic hy pogonadism has facilitated diagnosis of this and other similar cases. Histo pathology of a testicular biopsy and orchiectomy specimen in the younger br other revealed progressive loss of germinal epithelium with vacuolization o f postpubertal Sertoli cells suggesting an additional role for DAX-1 in tes ticular maturation and spermatogenesis, Application of genomic DNA analysis to both affected and nonaffected family members has enabled accurate diagn osis, significantly reduced anxiety, and allowed for appropriate counseling and improved patient care.