5-Alpha-reductase deficiency (5-ARD) is an autosomal recessive intersex condition caused by a mutation of the 5-alpha reductase type 2 gene.
5-Alpha-reductase is an enzyme that converts testosterone to dihydrotestosterone (DHT) in peripheral tissues. 5-Alpha-reductase deficiency-2 is biochemically characterized by low to low-normal levels of testosterone and decreased levels of 5α-DHT, creating a higher testosterone/DHT ratio.
DHT is a potent androgen, necessary for the development of male external genitalia in utero.
The condition affects only genetic males (that is, those with a Y chromosome) because DHT has no known role in female development.
Individuals with 5-ARD can have normal male external genitalia, ambiguous genitalia, or normal female genitalia. They are born with male gonads, including testicles and Wolffian structures, but usually appear to have female primary sex characteristics. As a consequence, they are often raised as girls, but usually have a male gender identity.
In general, individuals with 5-ARD are capable of producing viable sperm. In individuals with feminized or ambiguous genitalia, there is a tendency towards a macroclitoris or microphallus, and the urethra may attach to the phallus. This structure may be capable of ejaculations as well as erections, but may be insufficient for intercourse.
At puberty, individuals often have primary amenorrhoea, and may experience virilization. This may include descending of the testes, hirsutism (facial/body hair considered normal in males - not to be confused with hypertrichosis), deepening of the voice, and enlargement of the clitoris. In adulthood, individuals do not experience male-pattern baldness. As DHT is a far more potent androgen than testosterone alone, virilisation in those lacking DHT may be absent or reduced compared to males with functional 5-alpha reductase. It is hypothesized that rising testosterone levels at the start of puberty (around age twelve) are able to generate sufficient levels of DHT either by the action of 5-alpha-reductase type 1 (active in the adult liver, non-genital skin and some brain areas) or through the expression of low levels of 5-alpha-reductase type 2 in the testes.
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