Primary amenorrhea in four adolescents revealed 5α-reductase deficiency confirmed by molecular analysis.
OBJECTIVE
To determine the genetic cause of primary amenorrhea.


METHODS
Case series.


METHODS
Pediatric endocrinology, endocrinology, and gynecology departments of academic hospitals.


METHODS
Three adolescents and one young woman 46, XY patients with srd5A2 gene mutations.


METHODS
Genetic analysis of srd5A2.


RESULTS
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).


CONCLUSIONS
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.
Maimoun
Laurent
L
Service d'Hormonologie, Hôpital Lapeyronie, CHU Montpellier, and UMI Montpellier, Montpellier, France.
Philibert
Pascal
P
Bouchard
Philippe
P
Ocal
Gönül
G
Leheup
Bruno
B
Fenichel
Patrick
P
Servant
Nadège
N
Paris
Françoise
F
Sultan
Charles
C
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000568:Amenorrhea / Q000175:diagnosis* / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D055815:Young Adult
D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human