Homozygous CYP17A1 mutation (H373L) identified in a 46,XX female with combined 17α-hydroxylase/17,20-lyase deficiency

Background: Defects in cytochrome P450c17 are uncommon forms of congenital adrenal hyperplasia caused by CYP17A1 mutations. An H373L mutation in the CYP17A1 gene has been identified in Japanese and Chinese patients. This mutation impairs 17 alpha-hydroxylase and 17,20-lyase activity. Case: A 23-year-old Korean female (46,XX) presented with absent spontaneous puberty and hypertension. Hormonal findings were consistent with combined 17 alpha-hydroxylase/17,20-lyase deficiency. Very high levels of progesterone and 11-deoxycorticosterone were detected, coincident with normal 17-hydroxysteroid levels. Plasma levels of dehydroepiandrosterone, androstenedione and testosterone were extremely low. Mutation analysis of the CYP17A1 gene identified a homozygous missense mutation changing His (CAC) to Leu (CTC) at codon 373. This mutation is known to completely abolish both 17 alpha-hydroxylase and 17,20-lyase activity. The patient's nonconsanguineous parents were heterozygous for this mutation. Of note, her serum steroid levels indicated decreased, but still present, 17 alpha-hydroxylase activity in vivo. Conclusion: We detected a homozygous H373L mutation in a patient with combined 17 alpha-hydroxylase/17,20-lyase deficiency. Our findings demonstrate minimally preserved 17 alpha-hydroxylase activity in vivo and contribute to our knowledge of the regional prevalence of this mutation in Northeast Asia.