The Diagnosis and Management of an Adult 46xy Female with Isolated 17, 20-Lyase Deficiency due to a Novel Mutation P. Y35xi Cytochrome B5a Gene

Objective: To report the diagnosis and clinical management of an adult Chinese 46 XY woman due to isolated 17,20-lyase deficiency resulting from a homozygous Cytochrome B5A mutation p.Y35X with non-consanguineous parents. Design: Case Report. Setting: Gynaecological endocrine clinic in a University Hospital. Patients: A 29 year-old Chinese woman with 46XY Disorder of Sex Development (DSD) resulting from isolated 17, 20-lyase deficiency and her parents. Intervention: Investigations with serum hormonal profiles, urine steroid profile, serum methaemoglobin, mutational analyses of the CYP17A1 and CYB5A by polymerase chain reaction (PCR) and DNA sequencing, surgical correction for ambiguous genitalia. Main outcome measure: Steroid hormones and methaemoglobin levels, urine steroid profile, serum mutational analyses of CYP17A1 and CYB5A genes and post-operative clinical outcomes. Result: Steroid hormone levels and urine steroid profile suggested isolated 17,20-lyase deficiency with elevated methaemoglobin level. Mutational analysis confirmed a homozygous novel mutation p.Y35X in the CYB5A gene. Correctional surgery restored normal female external genitalia. Conclusion: Urine steroid profiling is a useful test in pinpointing the exact error of testosterone metabolism and serum methaemoglobin level may be used to screen for abnormal Cytochrome B5 function. Surgical treatment aims at restoring normal external genitalia of the assigned gender.