Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency
https://doi.org/10.14341/probl201157325-30
Abstract
Type 3 17-beta hydroxysteroid dehydrogenase (17HSD3) deficiency is a rare form of abnormal sex formation (ASF) in 46XY subjects in which the conversion of androstendione to testosterone is blocked; this defect results in compromised masculinization of the external genitalia during the intrauterine development. A distinctive feature of this form of sex development is masculinization at puberty due to the extragonadal conversion of androstendione to testosterone. Two clinical cases are reported: both girls were born with the female-type of external genitalia and 46XY karyotype, but progressive virilization in the pubertal period gave reason to suspect diagnosis of 17HSD3 deficiency. In both cases, this diagnosis was confirmed in molecular genetic studies (the following mutations were identified in the HSD17B3 gene: c.728-734delGATAACCp.1244fsX254/c.277+4A>T and c.277+4A>T). These two cases are the first reports of 17HSD3 deficiency in the Russian literature.
References
1. George M.M., New M.I., Ten S. et al. The clinical and molecular heterogeneity of 17βHSD-3 enzyme deficiency. Horm Res Paediatr 2010;74:4:229-240.
2. Wu X., Lukacik P., Kavanagh K.L., Oppermann U. SDR-type human hydroxysteroid dehydrogenases involved in steroid hormone activation. Mol Cell Endocrinol 2007;265-266:71-76.
3. Moeller G., Adamski J. Integrated view on 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 2009;30:1-2:7-19.
4. Prehn C., Möller G., Adamski J. Recent advances in 17beta-hydroxysteroid dehydrogenases. J Steroid Biochem Mol Biol 2009;114:1-2:72-77.
5. Lukacik P., Kavanagh K.L., Oppermann U. Structure and function of human 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol 2006;248:1-2:61-71.
6. Geissler W.M., Davis D.L., Wu L. et al. Male pseudohermaphroditism caused by mutations of testicular 17-beta-hydroxysteroid dehydrogenase 3. Nat Genet 1994;7:1:34-39.
7. Lee Y.S., Kirk J.M., Stanhope R.G. et al. Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clin Endocrinol (Oxf) 2007;67:1:20-28.
8. Andersson S., Geissler W.M., Wu L. et al. Molecular genetics and pathophysiology of 17beta-hydroxysteroid dehydrogenase 3 deficiency. J Clin Endocrinol Metab 1996;81:1:130-136.
9. Mendonca B.B., Inacio M., Arnhold I.J. et al. Male pseudohermaphroditism due to 17beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, andmanagement. Medicine (Baltimore) 2000;79:5:299-309.
10. Boehmer A.L., Brinkmann A.O., Sandkuijl L.A. et al. 17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations. J Clin Endocrinol Metab 1999;84:12:4713-4721.
11. Ulloa-Aguirre A., Bassol S., Poo J. et al. Endocrine and biochemical studies in a 46,XY phenotypically male infant with 17-ketosteroid reductase deficiency. J Clin Endocrinol Metab 1985;60:4:639-643.
12. den Dunnen J.T., Antonarakis S.E. Nomenclature for the description of human sequence variations. Hum Genet 2001;109:1:121-124.
13. Saez J.M., Morera A.M., De Peretti E., Bertrand J. Further in vivo studies in male pseudohermaphroditism with gynecomastia due to a testicular 17-ketosteroid reductase defect (compared to a case of testicular feminization). J Clin Endocrinol Metab 1972;34:3:598-600.
14. Kohn G., Lasch E.E., Kosler A. Male pseudohermaphroditism with post-pubertal gender role reversal in a large Arab kindred. 6th International Congress. Hum Genet (Jerusalem) 1981;259.
15. Rösler A., Silverstein S., Abeliovich D. (R80Q) mutation in 17beta-hydroxysteroid dehydrogenase type 3 gene among Arabs of Israel is associated with pseudohermaphroditism in males and normal asymptomatic females. J Clin Endocrinol Metab 1996;81:5:1827-1831.
16. Rosler A. 17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population. Pediatr Endocrinol Rev 2006;3:Suppl 3:455-461.
17. Mains L.M., Vakili B., Lacassie Y. et al. 17beta-hydroxysteroid dehydrogenase 3 deficiency in a male pseudohermaphrodite. Fertil Steril 2008;89:1:228:e213-e227.
18. Youssoufian H. Natural gene therapy and the Darwinian legacy. Nat Genet 1996;13:3:255-256.
19. Can S., Zhu Y.S., Cai L.Q. et al. The identification of 5α-reductase-2 and17beta-hydroxysteroid dehydrogenase-3 gene defects in male pseudohermaphrodites from a Turkish kindred. J Clin Endocrinol Metab 1998;83:2:560-569.
20. Ademola Akesode F., Meyer W.J., Migeon C.J. Male pseudohermaphroditism with gynaecomastia due to testicular 17-ketosteroid reductase deficiency. Clin Endocrinol (Oxford) 1977;7:6:443-452.
21. Faisal Ahmed S., Iqbal A., Hughes I.A. The testosterone: androstenedione ratio in male undermasculinization. Clin Endocrinol (Oxford) 2000;53:6:697-702.
22. Farkas A., Rosler A. Ten years experience with masculinizing genitoplasty in male pseudohermaphroditism due to 17beta-hydroxysteroid dehydrogenase deficiency. Eur J Pediatr 1993;152:Suppl 2:S88-S90.
23. Castro-Magana M., Angulo M., Uy J. Male hypogonadism with gynecomastia caused bylate-onset deficiency of testicular 17-ketosteroidreductase. N Engl J Med 1993;328:18:1297-1301.
24. Balducci R., Toscano V., Wright F. et al. Familial male pseudohermaphroditism with gynaecomastia due to 17beta-hydroxysteroid dehydrogenase deficiency. A report of 3 cases. Clin Endocrinol (Oxford) 1985;23:4:439-444.
25. Bertelloni S., Dati E., Hiort O. Diagnosis of 17beta-hydroxysteroid dehydrogenase deficiency. Exp Rev Endocrinol Metab 2009;4:53-65.
26. Twesten W., Holterhus P., Sippell W.G. et al. Clinical, endocrine, and molecular genetic findings in patients with 17beta-hydroxysteroid dehydrogenase deficiency. Horm Res 2000;53:1:26-31.
27. Hiort O., Reinecke S., Thyen U. et al. Puberty in disorders of somatosexual differentiation. J Pediatr Endocrinol Metab 2003;16:Suppl 2:297-306.
Review
For citations:
Kolodkina A.A., Kalinchenko N.I., Nizhnik A.N., Nokel' M.A., Tiul'pakov A.N. Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency. Problems of Endocrinology. 2011;57(3):25-30. (In Russ.) https://doi.org/10.14341/probl201157325-30
Views:
849
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
.jpg){kind=logo}
