Unmasking a rare variant: 17β-HSD3 deficiency in a male infant with disorders of sex development.

17-beta hydroxysteroid dehydrogenase-3 enzyme is an enzyme expressed almost exclusively in the testes; it plays a crucial role in gonadal differentiation by catalysing the conversion of androstenedione (Δ4) to testosterone (T). The enzyme is encoded by the 17-B-hydroxysteroid dehydrogenase-3 (HSD17B3) gene. Mutations in this gene result in undervirilisation of the external male genitalia. We present a case of a child born with ambiguous genitalia. The gonads were palpable in the inguinal canal bilaterally and their presence was confirmed by ultrasound. This raised the suspicion of 46XY disorder of sex development. Initial biochemical investigations showed a low T/Δ4 ratio, which normalised following human chorionic gonadotropin stimulation, supporting the diagnosis of a steroidogenic defect. Due to the initially very low ratio, genetic testing was pursued and revealed a homozygous mutation in the HSD17B3 gene, c.608C>T (p.Ala203Val) near exon 9. This variant has been reported only once previously in the literature.