17β-Hydroxysteroid dehydrogenase III deficiency

17β-Hydroxysteroid dehydrogenase III deficiency (17β-HSD3 deficiency) is a rare endocrine disorder affecting the biosynthesis of testosterone, an important hormone in the development of male sexual characteristics. This condition is part of a group of disorders known as intersex conditions, which involve discrepancies between the external genitals and the genetic sex.

Overview

17β-HSD3 deficiency is caused by mutations in the HSD17B3 gene, which encodes the 17β-hydroxysteroid dehydrogenase type 3 enzyme. This enzyme plays a crucial role in the steroidogenesis pathway, converting androstenedione (an androgen precursor) into testosterone. When the activity of this enzyme is impaired due to genetic mutations, the production of testosterone is significantly reduced, leading to the development of female external genitalia in genetically male individuals (46,XY karyotype).

Symptoms and Diagnosis

Individuals with 17β-HSD3 deficiency are typically assigned female at birth due to the presence of female-like external genitalia. However, at puberty, virilization may occur, including the development of male secondary sexual characteristics such as increased muscle mass, deepening of the voice, and growth of facial hair. Some individuals may also experience cryptorchidism (undescended testes) or have a small phallus.

Diagnosis is usually made through a combination of clinical examination, hormone assays (showing elevated levels of androstenedione and low levels of testosterone), and genetic testing for mutations in the HSD17B3 gene.

Treatment

Treatment for 17β-HSD3 deficiency is tailored to the individual's needs and may include hormone replacement therapy (HRT) to address hormone imbalances and surgical interventions to modify the appearance of the genitalia if desired by the individual. Psychological support is also an important aspect of treatment, given the complex issues related to gender identity and psychosocial well-being.

Epidemiology

17β-HSD3 deficiency is a very rare condition, with a higher prevalence reported in certain populations due to the founder effect, such as in the Gaza Strip. The exact incidence worldwide is unknown.

See Also

• Intersex
• Steroidogenesis
• Hormone replacement therapy
• Cryptorchidism

NIH genetic and rare disease info

• NIH info on 17β-Hydroxysteroid dehydrogenase III deficiency

17β-Hydroxysteroid dehydrogenase III deficiency is a rare disease.