Clinical management and genetic variation analysis of patients with 17β-hydroxysteroid dehydrogenase deficiency

ContextDeficiency of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a rare autosomal recessive disorder of sex development affecting individuals with a 46, XY karyotype. It is caused by pathogenic variants in the HSD17B3 gene that impair the conversion of Δ4-androstenedione to testosterone.ObjectiveTo evaluate the clinical presentation and management of a female patient who exhibited masculinization during puberty and assess her long-term life satisfaction during follow-up.MethodsA female patient who exhibited masculinization during puberty underwent comprehensive endocrinological and genetic assessments. Subsequently, she underwent sex reassignment surgery and follow-up investigation.ResultsHormonal findings showed a baseline testosterone/androstenedione ratio of 1.77, which decreased to 1.32 after human chorionic gonadotropin stimulation; these findings are atypical for the diagnosis. Subsequently, compound heterozygous mutation p.I60 T(c.179T > C) and exon 1 deletion were identified. After extensive counseling, the patient's parents decided to reverse the patient's sex to male. Orchidopexy and two-stage urethroplasty were performed; histological evaluation demonstrated no malignancies of the testicular tissue. Follow-up after 1 year indicated that the patient was satisfied with their sex assignment.ConclusionsThe management of pediatric patients with rare 17β-HSD3 deficiency remains challenging. For patients diagnosed early, premature removal of the gonads is not recommended as the risk of malignancy is very low. Any decision must be carefully discussed within a multidisciplinary disorders of sex development team, together with the patient and their parents. Long-term follow-up is required to assess the impact of the chosen option on future quality of life.