Steroid 5-alpha-reductase 2 deficiency, a 46,XY disorder of sexual development (DSD) , is an autosomal recessive condition in which 46,XY subjects with bilateral testes and normal testosterone formation have impaired virilization during embryogenesis due to defective conversion of testosterone to dihydrotestosterone [2,3]. The clinical manifestations, pathogenesis, diagnosis, and treatment of 5-alpha-reductase deficiency are reviewed here. Defects in testosterone biosynthesis and in androgen receptor function are discussed elsewhere. (See "Pathogenesis and clinical manifestations of disorders of androgen action" and "Diagnosis and treatment of disorders of the androgen receptor" and "Uncommon causes of congenital adrenal hyperplasia".)
46,XY individuals — The typical clinical features in 46,XY males with 5-alpha-reductase 2 deficiency are those reported in the two originally recognized families [2,3].
- The external genitalia usually are predominately female at birth, with the exception of clitoromegaly in some, so that most affected males are raised as females. A variable degree of virilization occurs at the time of puberty.
- The internal urogenital tract is male, consisting of epididymides, vasa deferentia, seminal vesicles, and ejaculatory ducts that empty into a blind-ending vagina. The absence of müllerian duct derivatives indicates that anti-müllerian hormone is produced and acts normally. (See "Normal sexual development".)
- Pubertal gynecomastia may occur, but does not persist into adulthood.
A wide spectrum of phenotypes was reported in a subsequent study of 55 patients with 5-alpha–reductase 2 deficiency including :
- Clitoromegaly was present in 27 (49 percent), microphallus in 18 (33 percent), and normal female external genitalia in only four (7.3 percent).
- 40 patients (72 percent) were initially assigned to female gender, and of these, five (12.5 percent) switched to male sex at puberty.