Identifying 17-β-HSD3 Deficiency in Patients with Karyotype 46,XY Misdiagnosed with Androgen Insensitivity Syndrome: A Pediatric Case Report

BACKGROUND Defects in androgen synthesis, such as 17-beta-hydroxysteroid dehydrogenase type 3 (17-ß-HSD3) deficiency, can lead to ambiguous genitalia in people with karyotype 46,XY due to impaired testosterone and dihydrotestosterone production. This condition may be initially diagnosed as androgen insensitivity syndrome (AIS), an X-linked disorder characterized by female external genitalia, absence of Mullerian structures, inguinal testes, and primary amenorrhea in adolescence. This report describes the case of a 13-year-old phenotypic female with 46,XY karyotype and a history of virilization due to 17-ß-HSD3 deficiency, previously diagnosed with AIS. CASE REPORT We report the case of a 13-year-old phenotypic female who was initially diagnosed with AIS during early childhood at a rural hospital. Several years later, she presented to a pediatric endocrinology clinic with progressive signs of virilization, including hirsutism, deepening of the voice, and severe facial acne. Laboratory evaluation, including a human chorionic gonadotropin (hCG) stimulation test, revealed a markedly low testosterone-to-androstenedione (T/AND) ratio of 0.1, strongly suggestive of 17ß-HSD3 deficiency. Whole-exome sequencing identified a homozygous missense variant of uncertain significance in exon 4 of the HSD17B3 gene. As the patient had been raised as a female, the parents chose to maintain her female gender assignment. Subsequently, the patient underwent bilateral orchiectomy along with clitoroplasty and labioplasty at another medical center. CONCLUSIONS Genetic and hormonal testing play a crucial role in differentiating among various types of disorders of sex development, thereby reducing the risk of diagnostic uncertainty. Early referral to a pediatric endocrinologist is essential to ensure accurate diagnosis and appropriate management of affected individuals.