17-Hydroxylase/17,20-lyase defiency, 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-hydroxylase/17,20-lyase deficiency due to a novel homozygous mutation of CYP17.

A 20-year old female Turkish patient (46, XX) presented with primary amenorrhea, sexual infantilism, and easy fatiguability. The patient's steroid metabolism showed increased levels of mineralocorticoid precursors, and low or undetectable plasma concentrations of 17-hydroxycorticoids, androgens, and estrogens before and after ACTH stimulation. The gas chromatography-mass spectrometry (GC-MS) urinary steroid profile was dominated by metabolites of corticosterone and its precursors while cortisol and C₁₉-steroid metabolites were lacking. ACTH, FSH, and LH levels were elevated. These hormonal findings were consistent with a combined and total 17-hydroxylase/17,20-lyase deficiency. A therapy with hydrocortisone and a cyclic estrogen/gestagen substitution was initiated. The CYP17 gene analysis revealed homozygosity of the mutation Y27Stop (TAC TAA) in exon 1, a mutation, which has not been previously described. This novel mutation leads to a stop codon causing a total loss of 17-hydroxlyase/17,20-lyase activity, as reflected biochemically by the detected concentrations of the steroid metabolites.