ReviewReprint of “Steroid 5α-reductase 2 deficiency”

- 46,XY due 5α-reductase type 2 deficiency subjects have a variable degrees of external genitalia virilisation but most of them have almost normal female external genitalia at birth leading to female sex assignment.
- All patients virilise at puberty and gynecomastia is rarely observed in 5α-reductase type 2 deficiency patients.
- 5α-reductase type 2 deficiency is caused by homozygous or compound heterozygous loss-of-function mutations of the SRD5A2 gene.
- Normal testosterone to dihydrotestosterone ratio in affected patients indicates mutational analysis of the SRD5A2 gene as the first approach to 5α-reductase type 2 deficiency diagnoses, especially in neonates.
- Mutational analysis of the SRD5A2 gene is clinically important as the diagnosis of SRD5A2 mutations in neonates with atypical genitalia suggest the choice of male sex-of-rearing considering: the frequent change to male social sex, the better quality of life and the possibility of fertility following assisted reproduction techniques in the male social sex individuals.

Dihydrotestosterone is a potent androgen metabolite formed from testosterone by action of 5α-reductase isoenzymes. Mutations in the type 2 isoenzyme cause a disorder of 46,XY sex development, termed 5α-reductase type 2 deficiency and that was described forty years ago. Many mutations in the encoding gene have been reported in different ethnic groups. In affected 46,XY individuals, female external genitalia are common, but Mullerian ducts regress, and the internal urogenital tract is male. Most affected males are raised as females, but virilization occurs at puberty, and male social sex develops thereafter with high frequency. Fertility can be achieved in some affected males with assisted reproduction techniques, and adults with male social sex report a more satisfactory sex life and quality of life as compared to affected individuals with female social sex.