A case series published in 2026 in the Journal of Pediatric Endocrinology and Metabolism describes three cases with genetic confirmation of 17β-hydroxysteroid dehydrogenase type 3 deficiency (HSD17B3), a rare cause of differences of sex development (46,XY DSD) that may be accompanied by gender-related distress.
Genetic basis
Molecular analysis identified three distinct variants in the HSD17B3 gene: c.72C>A (p.Cys24Ter), c.764C>T (p.Ser255Leu) and c.607-1G>A (splice site). Two of them are novel variants that had not been described previously, expanding knowledge about the molecular spectrum of this enzymatic disorder.
Clinical relevance
This type of enzyme deficiency disrupts testosterone synthesis and can result in female-appearing external genitalia at birth in individuals with a 46,XY karyotype, with the consequent impact on gender assignment and subsequent identity development. Early molecular identification is key to appropriate multidisciplinary management.
The authors emphasize the importance of accurate genetic diagnosis to guide treatment and counseling, and point out the need for coordinated endocrinological and psychological follow-up.
Bibliographic reference: Rare phenotypic spectrum of 17β-hydroxysteroid dehydrogenase type 3 deficiency: case series from infancy to adolescence. Journal of Pediatric Endocrinology and Metabolism, 2026. PMID: 41580999.
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