5α-Reductase 2 deficiency

5α-Reductase 2 deficiency (5αR2D) is an autosomal recessive condition caused by mutations impairing the function of SRD5A2, a gene located on chromosome 2 and encoding the enzyme 5α-reductase type 2 (5αR2). 5αR2 is expressed in specific tissues and catalyzes the transformation of testosterone (T) to 5α-dihydrotestosterone (DHT). DHT plays a key role in the process of sexual differentiation.

This rare deficiency causes atypical sex development in genetic males (people with a 46XY karyotype), with a broad spectrum of presentations most apparent in the genitalia. Many people with 5-alpha reductase deficiency are assigned female at birth based on their external genitalia. In other cases, affected infants are assigned male at birth based on their external genitalia, often an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias). Still other affected infants may be assigned either female or male at birth as their external genitalia do not look clearly male or clearly female.

During puberty, an increase in the levels of male sex hormones leads to the development of some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair, and a growth spurt. The penis and scrotum may grow larger. People with 5-alpha reductase deficiency do not develop much facial or body hair.