17α‑hydroxylase/17,20‑lyase deficiency in congenital adrenal hyperplasia: A case report

Xu,Simiao; Hu,Shuhong; Yu,Xuefeng; Zhang,Muxun; Yang,Yan

doi:10.3892/mmr.2016.6029

17α‑hydroxylase/17,20‑lyase deficiency in congenital adrenal hyperplasia: A case report

Authors:
- Simiao Xu
- Shuhong Hu
- Xuefeng Yu
- Muxun Zhang
- Yan Yang
View Affiliations

Affiliations: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: December 12, 2016 https://doi.org/10.3892/mmr.2016.6029
Pages: 339-344
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 (CYP17A1) gene located on chromosome 10q24.3, which leads to a deficiency in 17α‑hydroxylase/17,20‑lyase. The disorder is characterized by low blood levels of estrogens, androgens and cortisol, which leads to a compensatory increase in adrenocorticotropic hormone levels that stimulate the production of mineralocorticoid precursors. This subsequently leads to hypertension, hypokalemia, primary amenorrhea and sexual infantilism. Over 90 distinct genetic lesions have been identified in patients with this disorder. The prevalence of common mutation of CYP17A1 gene differs among ethnic groups. Treatment of this disorder involves replacement of glucocorticoids and sex steroids. Estrogen alone is prescribed for patients who are biologically male with 17α‑hydroxylase deficiencies that identify as female. However, genetically female patients may receive estrogen and progesterone supplementation. In the present study, a 17‑year‑old female with 17α‑hydroxylase/17,20‑lyase deficiency that presented with primary amenorrhea and sexual infantilism and no hypertension, was examined. The karyotype of the patient was 46, XX, and genetic analysis revealed the presence of a compound heterozygous mutation in exons 6 and 8, leading to the complete absence of 17α‑hydroxylase/17,20‑lyase activity. The patient was treated with prednisolone and ethinyl estradiol. In addition, a summary of the recent literature regarding CAH is presented.

View Figures

View References

1	Honour JW: Diagnosis of diseases of steroid hormone production, metabolism and action. J Clin Res Pediatr Endocrinol. 1:209–226. 2009. View Article : Google Scholar : PubMed/NCBI
2	Miller WL and Auchus RJ: The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 32:81–151. 2011. View Article : Google Scholar : PubMed/NCBI
3	Krone N and Arlt W: Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 23:181–192. 2009. View Article : Google Scholar : PubMed/NCBI
4	Biason-Lauber A, Boscaro M, Mantero F and Balercia G: Defects of steroidogenesis. J Endocrinol Invest. 33:756–766. 2010. View Article : Google Scholar : PubMed/NCBI
5	Auchus RJ: The genetics, pathophysiology, and management of human deficiencies of P450c17. Endocrinol Metab Clin North Am. 30101–119. (vii)2001.PubMed/NCBI
6	Miller WL: Androgen synthesis in adrenarche. Rev Endocr Metab Disord. 10:3–17. 2009. View Article : Google Scholar : PubMed/NCBI
7	Miller WL: Steroid 17alpha-hydroxylase deficiency-not rare everywhere. J Clin Endocrinol Metab. 89:40–42. 2004. View Article : Google Scholar : PubMed/NCBI
8	Oh YK, Ryoo U, Kim D, Cho SY, Jin DK, Yoon BK, Lee DY and Choi D: 17alpha-hydroxlyase/17, 20-lyase deficiency in three siblings with primary amenorrhea and absence of secondary sexual development. J Pediatr Adolesc Gynecol. 25:e103–e105. 2012. View Article : Google Scholar : PubMed/NCBI
9	Miller WL: Congenital adrenal hyperplasias. Endocrinol Metab Clin North Am. 20:721–749. 1991.PubMed/NCBI
10	Kater CE and Biglieri EG: Disorders of steroid 17 alpha-hydroxylase deficiency. Endocrinol Metab Clin North Am. 23:341–357. 1994.PubMed/NCBI
11	Yanase T, Simpson ER and Waterman MR: 17 alpha-hydroxylase/17,20-lyase deficiency: From clinical investigation to molecular definition. Endocr Rev. 12:91–108. 1991. View Article : Google Scholar : PubMed/NCBI
12	Biglieri EG, Herron MA and Brust N: 17-hydroxylation deficiency in man. J Clin Invest. 45:1946–1954. 1966. View Article : Google Scholar : PubMed/NCBI
13	Matteson KJ, Picado-Leonard J, Chung BC, Mohandas TK and Miller WL: Assignment of the gene for adrenal P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase) to human chromosome 10. J Clin Endocrinol Metab. 63:789–791. 1986. View Article : Google Scholar : PubMed/NCBI
14	Picado-Leonard J and Miller WL: Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): Similarity with the gene for P450c21. DNA. 6:439–448. 1987. View Article : Google Scholar : PubMed/NCBI
15	Miller WL: The syndrome of 17,20 lyase deficiency. J Clin Endocrinol Metab. 97:59–67. 2012. View Article : Google Scholar : PubMed/NCBI
16	Turcu AF and Auchus RJ: The next 150 years of congenital adrenal hyperplasia. J Steroid Biochem Mol Biol. 153:63–71. 2015. View Article : Google Scholar : PubMed/NCBI
17	Goldsmith O, Solomon DH and Horton R: Hypogonadism and mineralocorticoid excess. The 17-hydroxylase deficiency syndrome. N Engl J Med. 277:673–677. 1967. View Article : Google Scholar : PubMed/NCBI
18	Larson A, Nokoff NJ and Travers S: Disorders of sex development: Clinically relevant genes involved in gonadal differentiation. Discovery medicine. 14:301–309. 2012.PubMed/NCBI
19	Philip J, Anjali, Thomas N, Rajaratnam S and Seshadri MS: 17-Alpha hydroxylase deficiency: An unusual cause of secondary amenorrhoea. Aust N Z J Obstet Gynaecol. 44:477–478. 2004. View Article : Google Scholar : PubMed/NCBI
20	Kim YM, Kang M, Choi JH, Lee BH, Kim GH, Ohn JH, Kim SY, Park MS and Yoo HW: A review of the literature on common CYP17A1 mutations in adults with 17-hydroxylase/17,20-lyase deficiency, a case series of such mutations among Koreans and functional characteristics of a novel mutation. Metabolism. 63:42–49. 2014. View Article : Google Scholar : PubMed/NCBI
21	Zhang M, Sun S, Liu Y, Zhang H, Jiao Y, Wang W and Li X: New, recurrent and prevalent mutations: Clinical and molecular characterization of 26 Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency. J Steroid Biochem Mol Biol. 150:11–16. 2015. View Article : Google Scholar : PubMed/NCBI
22	Hahm JR, Kim DR, Jeong DK, Chung JH, Lee MS, Min YK, Kim KW and Lee MK: A novel compound heterozygous mutation in the CYP17 (P450 17alpha-hydroxylase) gene leading to 17alpha-hydroxylase/17,20-lyase deficiency. Metabolism. 52:488–492. 2003. View Article : Google Scholar : PubMed/NCBI
23	Fardella CE, Zhang LH, Mahachoklertwattana P, Lin D and Miller WL: Deletion of amino acids Asp487-Ser488-Phe489 in human cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency. J Clin Endocrinol Metab. 77:489–493. 1993. View Article : Google Scholar : PubMed/NCBI
24	Kim SM and Rhee JH: A case of 17 alpha-hydroxylase deficiency. Clin Exp Reprod Med. 42:72–76. 2015. View Article : Google Scholar : PubMed/NCBI
25	Marsh CA and Auchus RJ: Fertility in patients with genetic deficiencies of cytochrome P450c17 (CYP17A1): Combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,20-lyase deficiency. Fertil Steril. 101:317–322. 2014. View Article : Google Scholar : PubMed/NCBI
26	Levran D, Ben-Shlomo I, Pariente C, Dor J, Mashiach S and Weissman A: Familial partial 17,20-desmolase and 17alpha-hydroxylase deficiency presenting as infertility. J Assist Reprod Genet. 20:21–28. 2003. View Article : Google Scholar : PubMed/NCBI