Purpose: The presentations of 17β-hydroxysteroid dehydrogenase type 3 deficiency, 5α-reductase type 2 deficiency, and complete androgen insensitivity snydrome can be clinically similar. However, individuals with 17β-hydroxysteroid dehydrogenase type 3 and 5α-reductase type 2 deficiencies will undergo pubertal virilization and should undergo gonadectomy prior to the age of maturation if reared in the female gender. The decision of when to perform gonadectomy among individuals with complete androgen insensitivity remains controversial. Proponents of delayed gonadectomy suggest that endogenous estrogen results in natural breast development and improved bone health. Proponents of early gonadectomy suggest that individuals are at increased risk of gonadal malignancy if the testes are left in situ.
Methods: Two sisters were initially diagnosed with complete androgen insensitivity snydrome as young children after testes were discovered during hernia surgery. A decision was made to delay gonadectomy. Virilization occurred in both individuals during puberty, and a diagnosis of 17β-hydroxysteroid dehydrogenase type 3 deficiency was made. Their cases were reviewed and gene sequencing was used to confirm their correct diagnoses.
Results: Confirmatory diagnosis through gene sequencing identified a heterozygous mutation for both a known splicing mutation and a previously unreported amplification mutation of the HSD17B3 gene. Gonadectomy was performed and vaginal dilations were used to achieve results satisfactory for potential sexual intercourse.
Conclusion: Differentiating 46,XY disorders of sex development is difficult. Failure to make the proper diagnosis may result in unwanted virilization. Any individual with a low testosterone:androstenedione ratio after hCG stimulation should undergo confirmatory genetic analysis of the HSD17B3 gene. The authors identified a previously unreported amplification mutation of the HSD17B3 gene. If a diagnosis of 17β-hydroxysteroid dehydrogenase type 3 deficiency is made in a child that is being reared female, gonadectomy is warranted to prevent virilization at the time of puberty. Furthermore, it is essential to obtain confirmatory diagnosis in any individual suspected of having complete androgen insensitivity syndrome before decision is made to postpone gonadectomy.