Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency

Ahmed Khattab, Tony Yuen, Mabel Yau, Sorahia Domenice, Elaine Maria Frade Costa, Kazmi Diya, Dwaipayan Muhuri, Christian Enrique Pina, Mirian Yumie Nishi, Amy C. Yang, Berenice Biharinho De Mendoncą, Maria I. New

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Steroid 17β-hydroxysteroid dehydrogenase III (17β-HSD3) deficiency is a rare autosomal recessive disorder that usually presents in patients with a 46,XY karyotype with ambiguous genitalia at birth. The 17β-HSD3 enzyme, which is encoded by the HSD17B3 gene, converts gonadal delta-4 androstenedione (Δ4) to testosterone (T). Such 17β-HSD3 enzyme deficiency is expected to lead to an increased ratio of D4 to T when the patient undergoes a human chorionic gonadotropin stimulation (hCG) test. Two patients with 46,XY disorders of sexual differentiation were studied. Serum D4 and T levels were measured by HPLC tandem mass spectrometry. As one of the patients was born to consanguineous parents, we performed single nucleotide polymorphism (SNP) microarray to analyze regions of homozygosity (ROH). The HSD17B3 gene was sequenced using the Sanger method. Contrary to expectations, both patients demonstrated decreased D4/T ratio after hCG stimulation. Initial sequencing results for the androgen receptor or 5α-reductase were negative for mutations. ROH analysis identified HSD17B3 as a candidate gene that might cause the disease. Sanger sequencing of the HSD17B3 gene confirmed 17β-HSD3 deficiency in both patients. Serum D4/T ratios are not reliable parameters for the diagnosis of 17β-HSD3 deficiency. Molecular genetic analysis provides accurate diagnosis.

Original languageEnglish
Pages (from-to)623-628
Number of pages6
JournalJournal of Pediatric Endocrinology and Metabolism
Issue number5-6
StatePublished - 1 May 2015


  • 17β-HSD3
  • HSD17B3
  • androstendione
  • hCG
  • testosterone


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