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17β-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up

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Abstract

Background

Deficiency of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a rare autosomal recessive 46,XY disorder of sex development (DSD). It is due to pathogenetic variants in the HSD17B3 gene. Mutated genes encode an abnormal enzyme with absent or reduced ability to convert Δ4-androstenedione (Δ4-A) to testosterone (T) in the fetal testis. Affected individuals are usually raised as females and diagnosis is made at puberty, when they show virilization.

Methods

A girl with a presumptive diagnosis of complete androgen insensitivity syndrome underwent endocrine and genetic assessment. Long-term follow-up was reported.

Results

The diagnosis of 17β-HSD3 deficiency was made (stimulated T/Δ4-A ratio: 0.15; HSD17B3 gene analysis: c.277+4A>T in intron 3/c.640_645del (p.Glu214_Glu215del) in exon 9. After extensive information, parents decided to maintain female sex. Gonadal removal was performed and histological evaluation demonstrated deep fibrosis of testicular tissue. Follow-up till 8.5 years of age showed somatic and neuro-psychological development fitting with the female sex.

Conclusions

Management of a child with the rare 17β-HSD3 deficiency remains challenging. Any decision must be carefully evaluated with parents. Long-term follow-up must be warranted by a multidisciplinary DSD team to evaluate the adequacy of the choices made on quality of life in later life.

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Funding

This study did not receive any specific fund or grant.

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Authors and Affiliations

  1. Pediatric Section, Department of Biomedical Sciences and Human Oncology, University “A. Moro” of Bari, Piazza G. Cesare, 11, 70124, Bari, Italy

    M. F. Faienza

  2. Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    F. Baldinotti

  3. UOC Chirurgia Pediatrica, Fondazione Policlinico Gemelli, Rome, Italy

    G. Marrocco

  4. Pediatric and Adolescent Endocrinology, Pediatric Unit, Department of Obstetrics, Gynecology and Paediatrics, Azienda Ospedaliero-Universitaria Pisana, Via Roma, 67, 56126, Pisa, Italy

    N. TyuTyusheva, D. Peroni, G. I. Baroncelli & S. Bertelloni

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  1. M. F. Faienza
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  4. N. TyuTyusheva
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  5. D. Peroni
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  6. G. I. Baroncelli
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Corresponding authors

Correspondence to M. F. Faienza or S. Bertelloni.

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The authors declare that they have no conflict of interest.

Ethical approval

For this type of study, clinical standard procedures for the investigation of people with DSD in our Departments were used, so that formal consent is not required. The clinical investigations were in accordance with the ethical standards of the Helsinki Declaration.

Informed consent

Written informed consent was obtained from the parents before any clinical procedures. No further measures were taken beyond those of routine clinical practice.

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Faienza, M.F., Baldinotti, F., Marrocco, G. et al. 17β-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up. J Endocrinol Invest 43, 1711–1716 (2020). https://doi.org/10.1007/s40618-020-01248-y

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