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5α-reductase deficiency is a rare autosomal recessive 46,XY disorder of sexual development (DSD) caused by mutations in the SRD5A2 gene, leading to deficient conversion of testosterone to dihydrotestosterone (DHT).

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https://www.youtube.com/watch?v=hklWoAyGeMM

This results in undervirilized external genitalia at birth, but normal male internal genitalia and often marked virilization at puberty.

Pathophysiology


Pathway Role
TestosteroneDHT Mediated by 5α-reductase type 2 (SRD5A2 gene)
DHT Critical for development of male external genitalia, prostate, and urethra
Deficiency Leads to ambiguous or female-like external genitalia, but normal Wolffian duct development (epididymis, vas deferens, seminal vesicles) due to intact testosterone action

Genetics:

Clinical Features


Neonatal / Childhood Presentation

Finding Description
Ambiguous genitalia Clitoromegaly, bifid scrotum, hypospadias
Female external genitalia In some, with no palpable gonads
No uterus Due to normal AMH production by Sertoli cells
Testes Usually located in inguinal canal or labioscrotal folds

Adolescence / Puberty

Finding Description
Virilization Deep voice, increased muscle mass, clitoromegaly or phallic growth, increased libido
No breast development Unlike AIS
Gender identity shift ~50–70% may transition to male gender role during or after puberty

Laboratory Evaluation


Test Finding
Testosterone Normal or elevated
DHT Low (key feature)
Testosterone:DHT ratio ↑↑ (>20–30) (hallmark)
LH/FSH May be normal or mildly elevated
AMH Normal (testicular function intact)
Karyotype 46,XY

Radiology