OBJECTIVE: To determine the genetic cause of primary amenorrhea.
DESIGN: Case series.
SETTING: Pediatric endocrinology, endocrinology, and gynecology departments of 
academic hospitals.
PATIENT(S): Three adolescents and one young woman 46, XY patients with srd5A2 
gene mutations.
MAIN OUTCOME MEASURE(S): Genetic analysis of srd5A2.
RESULT(S): We report four srd5A2 gene mutations in three adolescents and one 
young woman with 46,XY primary amenorrhea. All presented clitoromegaly and two 
presented hypospadias; all had been reared as females. Virilization of the 
external genitalia was noted in the pubertal period in all four patients. Three 
were maintained in the female sex of rearing by personal choice, and the fourth 
switched gender. We identified the homozygous substitutions p.L55Q (exon 1), 
p.Q56R (exon 1), and p.N193S (exon 4), in patients 1, 2, and 3, respectively. 
Patient 4 had compound heterozygous mutations, a new c.34delG (exon 1) 
associated with p.R246W (exon 5). All patients had high plasma T levels (ranges, 
16.2-23.2 nmol/L; normal female teenage range, 0.35-2 nmol/L).
CONCLUSION(S): Our data clearly demonstrate that 5α-reductase deficiency should 
be considered in XY adolescents with primary amenorrhea and no breast 
development associated with virilization at puberty and high plasma T. Positive 
parental consanguinity should reinforce the diagnostic orientation.