Male pseudohermaphroditism due to 5-alpha-reductase 2 deficiency

Male pseudohermaphroditism due to 5-alpha-reductase 2 deficiency is a rare intersex condition in which individuals with a 46,XY karyotype (typically associated with male sex) have ambiguous or female external genitalia at birth. This condition is a form of 5-alpha-reductase deficiency, a disorder affecting androgen metabolism. The enzyme 5-alpha-reductase type 2 is crucial for the conversion of testosterone to dihydrotestosterone (DHT), a more potent androgen responsible for the development of male external genitalia in utero. Deficiency in this enzyme leads to undermasculinization in XY individuals.

Etiology and Pathophysiology

The deficiency is caused by mutations in the SRD5A2 gene, which encodes the 5-alpha-reductase type 2 enzyme. These mutations lead to reduced or absent enzyme activity, resulting in insufficient production of DHT. Since DHT plays a key role in male genital development, its deficiency leads to ambiguous genitalia or a female external genital phenotype in individuals with a male genetic makeup.

Clinical Presentation

Individuals with this condition may be assigned female at birth due to the appearance of their genitalia. However, at puberty, the increased production of testosterone leads to virilization, including increased muscle mass, deepening of the voice, and growth of male external genitalia. It is often at this stage that the condition is diagnosed.

Diagnosis

Diagnosis is based on clinical evaluation, hormonal assays showing normal to elevated levels of testosterone with low levels of DHT, and genetic testing confirming mutations in the SRD5A2 gene. Imaging studies may also be conducted to assess internal reproductive structures.

Management and Treatment

Management of 5-alpha-reductase 2 deficiency is multidisciplinary, involving endocrinologists, urologists, and psychologists. Treatment may include hormone therapy to address deficiencies or imbalances and surgical interventions to modify the genitalia in line with the individual's gender identity. Psychological support is also crucial to address issues of gender identity, social integration, and personal well-being.

Prognosis

With appropriate medical and psychological support, individuals with male pseudohermaphroditism due to 5-alpha-reductase 2 deficiency can lead healthy and fulfilling lives. The prognosis largely depends on the timing of diagnosis and the initiation of treatment.

See Also

• Intersex
• Androgen Insensitivity Syndrome
• Disorders of Sex Development