5α-reductase 2 deficiency

A genetic condition affecting steroid metabolism

5α-Reductase 2 Deficiency
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Ambiguous genitalia, micropenis, hypospadias
Complications	N/A
Onset	Birth
Duration	Lifelong
Types	N/A
Causes	Mutations in the SRD5A2 gene
Risks	N/A
Diagnosis	Genetic testing, hormone analysis
Differential diagnosis	N/A
Prevention	N/A
Treatment	Hormone therapy, surgery
Medication	N/A
Prognosis	N/A
Frequency	Rare
Deaths	N/A

5α-Reductase 2 Deficiency is a rare genetic disorder that affects the metabolism of androgens, specifically the conversion of testosterone to dihydrotestosterone (DHT). This condition is caused by mutations in the SRD5A2 gene, which encodes the enzyme 5α-reductase type 2. This enzyme is crucial for the normal development of male external genitalia in utero.

Pathophysiology

The SRD5A2 gene provides instructions for making the enzyme 5α-reductase type 2, which is primarily expressed in the prostate, seminal vesicles, and skin. This enzyme converts testosterone, a potent androgen, into dihydrotestosterone (DHT), an even more potent androgen that is essential for the development of male external genitalia during embryogenesis. In individuals with 5α-reductase 2 deficiency, the lack of functional enzyme leads to reduced levels of DHT, resulting in incomplete masculinization of the external genitalia.

Clinical Presentation

Individuals with 5α-reductase 2 deficiency are typically born with ambiguous genitalia, which can include micropenis, hypospadias, and bifid scrotum. Internally, they possess male gonads (testes) and Wolffian duct structures, such as the vas deferens and seminal vesicles. At puberty, these individuals often experience virilization due to increased testosterone levels, which can lead to increased muscle mass, deepening of the voice, and growth of facial and body hair.

Diagnosis

Diagnosis of 5α-reductase 2 deficiency is based on clinical findings, hormone analysis, and genetic testing. Hormone analysis typically reveals elevated testosterone to DHT ratios. Genetic testing can confirm the diagnosis by identifying mutations in the SRD5A2 gene.

Management

Management of 5α-reductase 2 deficiency involves a multidisciplinary approach, including endocrinologists, urologists, and genetic counselors. Treatment options may include hormone therapy to promote masculinization or feminization, depending on the individual's gender identity. Surgical interventions may be considered to address ambiguous genitalia.

Prognosis

The prognosis for individuals with 5α-reductase 2 deficiency is generally good, with appropriate medical and surgical management. Individuals can lead healthy lives, although they may face challenges related to gender identity and social acceptance.

Also see

• Androgen Insensitivity Syndrome
• Congenital Adrenal Hyperplasia
• Intersex
• Dihydrotestosterone