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Steroid 5-alpha-reductase 2 deficiency

Olaf Hiort, MD
Section Editors
Peter J Snyder, MD
Alvin M Matsumoto, MD
Deputy Editor
Kathryn A Martin, MD


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 congenital adrenal hyperplasias", section on 'Lipoid 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 [4]. 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 [5] and Papua New Guinea [6], but steroid 5-alpha-reductase 2 deficiency is otherwise thought to be rare. The prevalence in the general population is unknown [7]. However, patients with steroid 5-alpha-reductase 2 deficiency have now been reported from a variety of countries and ethnic backgrounds [8-10].


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 [11]. Cloning of the cDNAs that encode the enzymes revealed that there are two steroid 5-alpha-reductases, termed types 1 and 2, involved in human sex development [12].

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Literature review current through: Nov 2017. | This topic last updated: Nov 06, 2017.
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