| 5-alpha-reductase deficiency | |
|---|---|
| Classification and external resources | |
5-alpha reductase produces dihydrotestosterone |
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| ICD-10 | E29.1, Q56.3 |
| ICD-9 | 257.2, 752.7 |
| OMIM | 264600 |
| DiseasesDB | 11 |
| eMedicine | ped/1980 |
5-Alpha-reductase deficiency (5-ARD) is an autosomal recessive intersex condition caused by a mutation of the 5-alpha reductase type 2 gene.[1]
Contents |
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.[2]
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 have female primary sex characteristics. As a consequence, they are often raised as girls, but usually have a male gender identity.[3][4]
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.[1] As DHT is a far more potent androgen than testosterone alone, virilization 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.
There is an increased risk of cryptorchidism in 5-ARD, causing infertility, but also a higher risk of testicular cancer. Fertility is further compromised by the underdevelopment of seminal vesicles and prostate.
On the other hand, fertility depending on female characteristics is impossible; although the external genitalia may be female, the vagina consists of only the lower two-thirds of a normal vagina, creating a blind-ending vaginal pouch. Due to the normal action of Müllerian inhibiting factor produced by the testes in utero, individuals with 5-ARD lack a uterus and Fallopian tubes. Thus, individuals with 5-ARD are not able to carry a pregnancy, and, since they have testes and not ovaries, they are unable to create ova, which precludes such infertility treatments as surrogate motherhood.
The number of people with this condition varies relative to geographic location, depending on how much of a given population is interrelated. In 1974, Jullianne Imperato-McGinley has estimated an incidence of 1:90 males in the Dominican Republic.[5]
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