Steroid 5-alpha-reductase 2 deficiency
- Olaf Hiort, MD
Olaf Hiort, MD
- University of Lübeck
- Section Editors
- Peter J Snyder, MD
Peter J Snyder, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Male Reproductive Endocrinology
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Alvin M Matsumoto, MD
Alvin M Matsumoto, MD
- Section Editor — Male Reproductive Endocrinology
- Professor of Medicine
- University of Washington School of Medicine
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 (DHT).
The clinical manifestations, pathogenesis, diagnosis, and treatment of 5-alpha-reductase deficiency are reviewed here. DSD due to 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".)
Steroid 5-alpha-reductase 2 deficiency was first reported in a pedigree of 24 families with 38 affected males in the Dominican Republic, an area where consanguineous marriages are common [1-3]. In a subsequent report of forty 46,XY infants born with ambiguous genitalia in the Dominican Republic over a 10-year period, five (13 percent) were diagnosed with steroid 5-alpha-reductase 2 deficiency . One of the five patients was traced to the original kindred of 38 affected subjects.
Additional clusters of patients have also been reported in Turkey  and Papua New Guinea , but steroid 5-alpha-reductase 2 deficiency is otherwise thought to be rare. The prevalence in the general population is unknown .
Individuals with steroid 5-alpha-reductase 2 deficiency are 46,XY with normal testosterone production but impaired virilization during embryogenesis, due to defective conversion of testosterone to dihydrotestosterone (DHT). The nature of the enzyme abnormality in this disorder was discovered when it was demonstrated that 5-alpha-reductase activity in cultured genital skin fibroblasts from affected subjects was reduced . Cloning of the cDNAs that encode the enzymes revealed that there are two steroid 5-alpha-reductases, termed types 1 and 2 .
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- CLINICAL MANIFESTATIONS
- 46,XY individuals
- - Gender-role change at puberty
- 46,XX individuals
- Laboratory assessment
- - Infants and prepubertal subjects
- - Adolescents and adults
- Differential diagnosis
- Initial gender assignment
- Raised as female and maintained female gender role
- Raised as males or changed gender role to male
- - Supplemental testosterone
- - Fertility
- SUMMARY AND RECOMMENDATIONS