17-beta hydroxysteroid dehydrogenase 3 (17βHSD3) converts androstendione to testosterone in the male testis. Testosterone is necessary for the development of the external male genitalia, a failure of which can result in sexual ambiguity.
We present a 22-year-old individual presenting with vaginal bleeding on attempted intercourse. At puberty (1314 years old), being brought up as a girl, she began to virilise alongside minimal breast development and primary amenorrhoea. On examination an android pelvis and XY pattern pubic hair was noted together with present labia majora and minora and cliteromegaly. Investigations confirmed bilateral inguinal testes (2.5×1.5 cm) and an absent uterus.
Biochemical analysis indicated an androstendione level of 53.9 nmol/l and testosterone level of 8.8 nmol/l, generating an abnormal androstendione:testosterone ratio of 6.125, which is suggestive of 17βHSD3 deficiency.
Genomic DNA was extracted from peripheral blood leukocytes from the above case and two normal, unrelated, controls. The 11 exons and splice sites of 17βHSD3 were amplified using PCR with subsequent sequence analyses. The patient appears to have deletions of exons 1 and 2, which showed positive amplification in the control cases. Southern blot analysis alongside RT-PCR and enzyme assays to determine the functional expression of the gene would constitute our further investigation; however we are limited by the wishes of the patient. It is planned to perform bilateral orchidectomies and then commence HRT.
In conclusion, we present an unusual case of vaginal bleeding, which after clinical, biochemical and genetic analysis lead to a diagnosis of 17βHSD3 deficiency due to deletions of exons 1 and 2. This is the first report in which an exon deletion has resulted in 17βHSD3 deficiency and a clinical case of intersexuality.