5α-Reductase Deficiency

5α-Reductase Deficiency is a rare genetic condition that affects the body's ability to produce a hormone called dihydrotestosterone (DHT), which is important for the development of male physical characteristics. This condition primarily impacts the reproductive system, especially in individuals who are genetically male (with XY chromosomes). People with this deficiency may be born with ambiguous or female-appearing external genitalia despite having male internal reproductive organs. During puberty, some male characteristics may develop due to increased testosterone, but the lack of DHT leads to incomplete masculinization. The condition can affect fertility and may cause challenges with gender identity and physical development. It is caused by mutations in the SRD5A2 gene, which encodes the enzyme responsible for converting testosterone to DHT.

5α-Reductase Deficiency is an autosomal recessive disorder caused by mutations in the SRD5A2 gene leading to deficient or absent activity of the 5α-reductase type 2 enzyme. This enzyme normally converts testosterone into the more potent androgen dihydrotestosterone (DHT), which is critical for the normal development of male external genitalia during fetal life. Affected individuals typically have a 46,XY karyotype but present with ambiguous genitalia or undervirilized external genitalia at birth, such as micropenis, hypospadias, or female-appearing genitalia. Internally, the Wolffian duct derivatives (epididymis, vas deferens, seminal vesicles) develop normally due to testosterone presence. At puberty, increased testosterone levels can induce partial virilization, including increased muscle mass and voice deepening, but external genitalia remain incompletely masculinized. The condition is significant for its role in disorders of sex development and may impact gender identity and fertility.