5-Alpha Reductase Deficiency

5-Alpha Reductase Deficiency is a 46,XY disorder of sex development (DSD) caused by reduced or absent function of the steroid 5-alpha reductase type 2 enzyme, which converts testosterone (T) into dihydrotestosterone (DHT) during embryogenesis. Individuals with 5-alpha reductase deficiency have normal Wolffian duct differentiation, but at birth the appearance of the external genitalia ranges from normal female to undermasculinized male. The classic presentation is ambiguous genitalia characterized by perineoscrotal hypospadias with pseudovagina, microphallus, and cryptorchidism. A recent study indicated that the most common phenotype is cliteromegaly, which was present in ~50% of individuals, followed by hypospadias associated with microphallus, which was reported in ~33% of patients (Maimoun et al., 2011). While most patients have ambiguous genitalia noted in infancy, individuals with female external genitalia may not present until puberty with primary amenorrhea, a lack of breast development, and virilization of the external genitalia. If the diagnosis of 5-alpha reductase deficiency is not made in infancy, the majority of infants are assigned a female gender based on the appearance of the external genitalia; however, significant virilization of the external genitalia occurs at puberty unless a gonadectomy is performed. An estimated 56-63% of individuals with 5-alpha reductase deficiency that are assigned a female gender have been reported to change to male gender identity at puberty (Cohen-Kettenis et al., 2005), so early diagnosis is important to assist with gender assignment. While most patients with 5-alpha reductase deficiency exhibit abnormally high levels of baseline and/or hCG-stimulated T:DHT ratios, individuals with partial enzyme deficiencies have been reported with normal T:DHT ratios. Therefore, in some cases it can be difficult to differentiate 5-alpha reductase deficiency from partial androgen insensitivity syndrome (AIS) and other 46,XY disorders of sex differentiation based on clinical and biochemical studies.

Tests Available

Forms and Documents

Test Details

  • Full gene sequencing for fetuses with prenatal ultrasound findings suggestive of 46,XY disorder of sex development
  • Mutation-specific testing for fetuses with a family history of known SRD5A2 mutations


2-3 weeks
20 mL Amniotic Fluid
20 mg CVS | 2 T25 flasks of cultured amniocytes | 2 T25 flasks of cultured chorionic villi | 3 Ug DNA Concentration

*Reporting times are typical, but could be extended in situations outside GeneDx's reasonable control.


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**The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.


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