5-alpha-reductase deficiency

5-Alpha-Reductase Deficiency

5-alpha-reductase deficiency is a rare genetic disorder that affects the development of male sexual characteristics. It is caused by mutations in the SRD5A2 gene, which encodes the enzyme 5-alpha-reductase type 2. This enzyme is responsible for converting testosterone into dihydrotestosterone (DHT), a more potent androgen that plays a crucial role in the development of male genitalia.

Genetics

5-alpha-reductase deficiency is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. Carriers, who have only one copy of the mutated gene, typically do not show symptoms.

Pathophysiology

In individuals with 5-alpha-reductase deficiency, the lack of DHT during fetal development leads to incomplete masculinization of the external genitalia. Affected individuals are genetically male (46,XY) but may be born with ambiguous genitalia or female-appearing genitalia. At puberty, increased testosterone levels can lead to virilization, with the development of male secondary sexual characteristics such as increased muscle mass, deepening of the voice, and growth of facial and body hair.

Clinical Presentation

The clinical presentation of 5-alpha-reductase deficiency can vary widely. Some individuals may have ambiguous genitalia at birth, while others may be raised as females and only discover their condition at puberty when they develop male secondary sexual characteristics. Common features include:

• Ambiguous genitalia
• Micropenis
• Hypospadias
• Bifid scrotum
• Absence of a prostate gland

Diagnosis

Diagnosis of 5-alpha-reductase deficiency is based on clinical findings, hormonal assays, and genetic testing. Hormonal assays typically show normal or elevated levels of testosterone with low levels of DHT. Genetic testing can confirm mutations in the SRD5A2 gene.

Management

Management of 5-alpha-reductase deficiency involves a multidisciplinary approach, including endocrinologists, urologists, and psychologists. Treatment options may include hormone replacement therapy, surgical correction of genital anomalies, and psychological support. The decision to raise an affected child as male or female can be complex and should involve careful consideration of the individual's phenotype, potential for virilization, and family preferences.

Prognosis

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

Also see

• Androgen Insensitivity Syndrome
• Congenital Adrenal Hyperplasia
• Intersex
• Sexual Differentiation