PRENATAL-DIAGNOSIS OF CONGENITAL LIPOID ADRENAL-HYPERPLASIA

Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare genetic d isorder of adrenal and gonadal steroidogenesis of unknown cause in whi ch cholesterol cannot be converted to pregnenolone. As a result, affec ted individuals can make no steroid hormones, so that all affected new borns are phenotypic females, irrespective of karyotype. We studied tw o pregnancies in a family with two previously affected children by exa mining fetal karyotype, genital ultrasonography, and amniotic fluid st eroid concentrations and by performing ACTH tests on family members. P renatal diagnosis correctly identified both an unaffected XX fetus and an affected XY fetus. In the affected pregnancy, amniotic fluid conce ntrations of progesterone and pregnenolone were 30% and 50% of normal, respectively, but concentrations of 17 alpha-hydroxypregnenolone, 17 alpha-hydroxyprogesterone, cortisol, dehydroepiandrosterone, androsten edione, and estriol were either extremely low or undetectable, suggest ing that these detected steroids were donated by maternal steroidogene sis. Fetal cord blood obtained at the termination of pregnancy showed very low concentrations of estrogens donated by the mother's circulati on. Absent fetal steroidogenesis was confirmed by gas chromatography a nd mass spectrometry of both fetal and maternal serum. The responses o f 10 different steroids to adrenal stimulation with ACTH in the obliga tely heterozygous parents were normal. Thus, unlike the case with othe r forms of CAH, heterozygosity cannot be determined by hormonal respon ses to provocative testing with ACTH. Immunocytochemistry and Western blotting showed that the affected placental tissue contained P450scc p rotein, confirming that P450scc is intact in these patients.