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Genotype–phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey

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Abstract

Background

Studies regarding genetic and clinical characteristics, gender preference, and gonadal malignancy rates for steroid 5-alpha-reductase type 2 deficiency (5α-RD2) are limited and they were conducted on small number of patients.

Objective

To present genotype–phenotype correlation, gonadal malignancy risk, gender preference, and diagnostic sensitivity of serum testosterone/dihydrotestosterone (T/DHT) ratio in patients with 5α-RD2.

Materials and methods

Patients with variations in the SRD5A2 gene were included in the study. Demographic characteristics, phenotype, gender assignment, hormonal tests, molecular genetic data, and presence of gonadal malignancy were evaluated.

Results

A total of 85 patients were included in the study. Abnormality of the external genitalia was the most dominant phenotype (92.9%). Gender assignment was male in 58.8% and female in 29.4% of the patients, while it was uncertain for 11.8%. Fourteen patients underwent bilateral gonadectomy, and no gonadal malignancy was detected. The most frequent pathogenic variants were p.Ala65Pro (30.6%), p.Leu55Gln (16.5%), and p.Gly196Ser (15.3%). The p.Ala65Pro and p.Leu55Gln showed more undervirilization than the p.Gly196Ser. The diagnostic sensitivity of stimulated T/DHT ratio was higher than baseline serum T/DHT ratio, even in pubertal patients. The cut-off values yielding the best sensitivity for stimulated T/DHT ratio were ≥ 8.5 for minipuberty, ≥ 10 for prepuberty, and ≥ 17 for puberty.

Conclusion

There is no significant genotype–phenotype correlation in 5α-RD2. Gonadal malignancy risk seems to be low. If genetic analysis is not available at the time of diagnosis, stimulated T/DHT ratio can be useful, especially if different cut-off values are utilized in accordance with the pubertal status.

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Acknowledgements

We would like to thank Feyza Darendeliler, Ömer Tarım, Aysun Bideci, Abdullah Bereket, Bilgin Yüksel, Murat Aydın, Yusuf Kenan Haspolat, Semra Çetinkaya, Teoman Akçay, and Ediz Yeşilkaya for their contributions to the study.

Funding

This work was supported financially by the Turkish Pediatric Endocrinology and Diabetes Society (Grant number: 032015).

Author information

Authors and Affiliations

  1. Department of Pediatric Endocrinology, Faculty of Medicine, Dokuz Eylül University, Balcova, 35340, Izmir, Turkey

    A. Abacı

  2. Department of Pediatric Endocrinology, Faculty of Medicine, İzmir Katip Çelebi University, Izmir, Turkey

    G. Çatlı

  3. Division of Genetics, Tepecik Training and Research Hospital, Sağlık Bilimleri University, Izmir, Turkey

    Ö. Kırbıyık

  4. Department of Pediatric Endocrinology, Faculty of Medicine and Dr Sami Ulus Woman Health and Children Research Hospital, Yıldırım Beyazıt University, Ankara, Turkey

    N. M. Şahin & Z. Aycan

  5. Department of Pediatric Endocrinology, Faculty of Medicine, İstanbul University, İstanbul, Turkey

    Z. Y. Abalı & F. Baş

  6. Department of Pediatric Endocrinology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey

    E. Ünal

  7. Department of Pediatric Endocrinology, Faculty of Medicine, Ankara University, Ankara, Turkey

    Z. Şıklar & M. Berberoğlu

  8. Department of Pediatric Endocrinology, Faculty of Medicine, Çukurova University, Adana, Turkey

    E. Mengen

  9. Department of Pediatric Endocrinology, Faculty of Medicine, Ege University, Izmir, Turkey

    S. Özen & Ş. Darcan

  10. Department of Pediatric Endocrinology, Faculty of Medicine, Marmara University, İstanbul, Turkey

    T. Güran

  11. Department of Pediatric Endocrinology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey

    C. Kara

  12. Division of Pediatric Endocrinology, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul, Turkey

    M. Yıldız

  13. Department of Pediatric Endocrinology, Faculty of Medicine, Uludağ University, Bursa, Turkey

    E. Eren

  14. Division of Pediatric Endocrinology, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey

    Ö. Nalbantoğlu

  15. Department of Pediatric Endocrinology, Göztepe Training and Research Hospital, İstanbul, Turkey

    A. Güven

  16. Department of Pediatric Endocrinology, Faculty of Medicine, Amasya University, Amasya, Turkey

    A. Güven

  17. Division of Pediatric Endocrinology, Erzurum Training and Research Hospital, Erzurum, Turkey

    A. Çayır

  18. Department of Pediatric Endocrinology, Faculty of Medicine, Gazi University, Ankara, Turkey

    E. D. Akbaş

  19. Department of Pediatric Endocrinology, Numune Training and Research Hospital, Sağlık Bilimleri University, Adana, Turkey

    Y. Kor

  20. Department of Pediatric Endocrinology, Sağlık Bilimleri University Antalya Training and Research Hospital, Antalya, Turkey

    Y. Çürek

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  1. A. Abacı
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Correspondence to A. Abacı.

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Abacı, A., Çatlı, G., Kırbıyık, Ö. et al. Genotype–phenotype correlation, gonadal malignancy risk, gender preference, and testosterone/dihydrotestosterone ratio in steroid 5-alpha-reductase type 2 deficiency: a multicenter study from Turkey. J Endocrinol Invest 42, 453–470 (2019). https://doi.org/10.1007/s40618-018-0940-y

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