17 alpha -Hydroxylase/17,20-Lyase Deficiency Caused by a Novel Homozygous Mutation (Y27Stop) in the Cytochrome CYP17 Gene

CONTEXT: 17 alpha -Hydroxylase/17,20-lyase deficiency, a rare autosomal recessive form of congenital adrenal hyperplasia, is caused by mutations in the cytochrome P450c17 (CYP17) gene. We report on a case of complete 17 alpha -hydroxylase/17,20-lyase deficiency due to a novel homozygous mutation of CYP17. DESIGN: A 20-yr-old female Turkish patient (46,XX) presented with primary amenorrhea, sexual infantilism, and easy fatigability. RESULTS: The patient's steroid metabolism showed increased levels of mineralocorticoid precursors and low or undetectable plasma concentrations of 17 alpha -hydroxycorticoids, androgens, and estrogens before and after ACTH stimulation. The gas chromatography-mass spectrometry urinary steroid profile was dominated by metabolites of corticosterone and its precursors, while cortisol and C sub(19)-steroid metabolites were lacking. ACTH, FSH, and LH levels were elevated. These hormonal findings were consistent with a combined and total 17 alpha -hydroxylase/17,20-lyase deficiency. A therapy with hydrocortisone and a cyclic estrogen/gestagen substitution was initiated. CONCLUSION: The CYP17 gene analysis revealed homozygosity of the mutation Y27Stop (TAC arrow right TAA) in exon 1, a mutation that has not been previously described. This novel mutation leads to a stop codon causing a total loss of 17 alpha -hydroxlyase/17,20-lyase activity, as reflected biochemically by the detected concentrations of the steroid metabolites.