Late diagnosis of 5alpha steroid-reductase deficiency due to IVS12A>G mutation of the SRD5a2 gene in an adolescent girl presented with primary amenorrhea.

BACKGROUND: The clinical spectrum of 5α-reductase deficiency, caused by mutations in the SRD5A2 gene, ranges from complete female appearance of the external genitalia at birth to nearly complete male phenotype.

CASE REPORT: A 14-year-old girl presented with primary amenorrhea (PA) and lack of breast development. She was 173 cm in height, had an increased amount of pubic hair and clitoromegaly (3 cm), with a 4 cm blind vaginal pouch. Gonads were palpable in the inguinal canal bilaterally and no uterus was identified on ultrasound. Chromosomal analysis showed a 46,XY karyotype. The Testosterone/DHT ratio was high (16.5) and further increased to 29.4 after stimulation with hCG, thus favouring the diagnosis of 5α-reductase deficiency. Since the issue of gender change was not considered, gonadectomy was performed followed by successful feminisation with hormonal replacement therapy.

GENETIC STUDIES: Molecular analysis of the SRD5A2 gene by DNA sequencing of all 5 exons revealed the presence of the splice mutation A>G at position -2 of the acceptor site of intron 1/exon 2 (IVS1-2A>G) in homozygosity. Both non-consanguineous parents were found to be heterozygotes for this mutation.

CONCLUSIONS: Although rare, SRD5A2 gene defect should be suspected in any girl presenting with PA and virilisation at puberty. The IVS1-2A>G mutation of the SRD5A2 gene predominates in Greek-Cypriot patients with 5α-reductase deficiency and very likely reflects a founder effect.