Definitive diagnosis of enzymatic deficiencies of steroidogenesis in at-risk newborns and infants by urinary marker analysis using GC/MS-SIM.

A simplified urinary marker analysis for diagnosis of congenital adrenal hyperplasia (CAH) and 5alpha-reductase deficiency in infancy by GC/MS-SIM is introduced. The analysis was performed in 161 patients aged 3-90 days, 99 females and 62 males. CAH due to 21-hydroxylase deficiency was diagnosed in 61 patients (42 females and 19 males; in 10 cases simple virilizing form and in 51 patients salt-wasting form) and CAH induced by 3beta-hydroxysteroid dehydrogenase deficiency without salt loss in 1 female patient. In 2 full-term newborns and 6 preterm infants, a false-positive diagnosis of CAH, which had been based on serum steroid evaluation, was made. In these cases, increased excretion of fetal adrenal zone steroids was confirmed as a possible source of false-positive serum 11-deoxycortisol and 17alpha-hydroxyprogesterone values. Lack of fetal adrenal zone steroid metabolites in 2 male newborns with salt loss symptoms led to the diagnosis of adrenal insufficiency due to X-linked adrenal hypoplasia and adrenal hemorrhage. A single analysis of urinary CAH markers by the very sensitive and selective GC/MS-SIM method can replace numerous assays of various steroids that must be carried out for positive diagnosis of abnormal steroidogenesis in infancy.