Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Case Report

Case Report: A Novel Mutation Leading to 11-β Hydroxylase Deficiency in a Female Patient

Author(s): Burak Ozbas, Mikail Demir, Huseyin Dursun, Izem Sahin, Aysa Hacioglu, Zuleyha Karaca, Munis Dundar and Kursad Unluhizarci*

Volume 23, Issue 5, 2023

Published on: 16 November, 2022

Page: [721 - 726] Pages: 6

DOI: 10.2174/1871530322666221007145410

open access plus

conference banner
Abstract

Background: 11β hydroxylase deficiency (11βOHD) ranks as the second most common enzyme deficiency that causes congenital adrenal hyperplasia. Depending on the severity of the enzyme deficiency, it can lead to cortisol deficiency, androgen excess and hypertension due to increased mineralocorticoid precursor levels. Many different types of mutations in the CYP11B1 gene located on chromosome 8q24.3 have been shown to cause 11βOHD. Here, we report a novel missense mutation that leads to 11βOHD in a female patient.

Case Presentation: A 35-year-old female patient was admitted to the Endocrinology Department with a complaint of abdominal pain. The patient had a history of genital reconstruction surgery twice in childhood. On physical examination, an abdominal mass was detected. Laboratory examination of the patient revealed low levels of cortisol, potassium and high levels of ACTH, 11-deoxycortisol and androstenedione, suggesting 11βOHD. Genotyping showed a novel homozygous missense mutation (c.1385T>C L462P variant) detected on the 8th chromosome where the CYP11B1 gene is located. Glucocorticoid therapy was commenced for the patient whose diagnosis of 11βOHD was confirmed by both hormonal and genetic tests. A mass originating from the left adrenal gland with the largest diameter of 7 cm was compatible with myelolipoma.

Conclusion: In this case report, we aimed to contribute to the literature by reporting a new missense mutation in the CYP11B1 gene, leading to classic type 11βOHD that has not been described before.

Keywords: Congenital adrenal hyperplasia, 11-beta hydroxylase deficiency, 11-deoxycortysol, CYP11B1 gene, mineralocorticoid pressure levels.

« Previous Next »
Graphical Abstract

[1]
Unluhizarci, K.; Kula, M.; Dundar, M.; Tanriverdi, F.; Israel, S.; Colak, R.; Dokmetas, H.S.; Atmaca, H.; Bahceci, M.; Balci, M.K.; Comlekci, A.; Bilen, H.; Akarsu, E.; Erem, C.; Kelestimur, F. The prevalence of non-classic adrenal hyperplasia among Turkish women with hyperandrogenism. Gynecol. Endocrinol., 2010, 26(2), 139-143.
[http://dx.doi.org/10.3109/09513590903215466] [PMID: 19718570]
[2]
Van Der Grinten, C.H.L.; Speiser, P.W.; Ahmed, S.F.; Arlt, W.; Auchus, R.J.; Falhammar, H.; Flück, C.E.; Guasti, L.; Huebner, A.; Kortmann, B.B.M.; Krone, N.; Merke, D.P.; Miller, W.L.; Nordenström, A.; Reisch, N.; Sandberg, D.E.; Stikkelbroeck, N.M.M.L.; Touraine, P.; Utari, A.; Wudy, S.A.; White, P.C. Congenital adrenal hyperplasia-current insights in pathophysiology, diagnostics, and management. Endocr. Rev., 2022, 43(1), 91-159.
[http://dx.doi.org/10.1210/endrev/bnab016] [PMID: 33961029]
[3]
El-Maouche, D.; Arlt, W.; Merke, D.P. Congenital adrenal hyperplasia. Lancet, 2017, 390(10108), 2194-2210.
[http://dx.doi.org/10.1016/S0140-6736(17)31431-9] [PMID: 28576284]
[4]
Polat, S.; Karaburgu, S.; Unluhizarci, K.; Dündar, M.; Özkul, Y.; Arslan, Y.K.; Karaca, Z.; Kelestimur, F. Comprehensive genotyping of Turkish women with hirsutism. J. Endocrinol. Invest., 2019, 42(9), 1077-1087.
[http://dx.doi.org/10.1007/s40618-019-01028-3] [PMID: 30811025]
[5]
Speiser, P.W.; Azziz, R.; Baskin, L.S.; Ghizzoni, L.; Hensle, T.W.; Merke, D.P.; Meyer, B.H.F.L.; Miller, W.L.; Montori, V.M.; Oberfield, S.E.; Ritzen, M.; White, P.C. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab., 2010, 95(9), 4133-4160.
[http://dx.doi.org/10.1210/jc.2009-2631] [PMID: 20823466]
[6]
Bulsari, K.; Falhammar, H. Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Endocrine, 2017, 55(1), 19-36.
[http://dx.doi.org/10.1007/s12020-016-1189-x] [PMID: 27928728]
[7]
Yau, M.; Haider, S.; Khattab, A.; Ling, C.; Mathew, M.; Zaidi, S.; Bloch, M.; Patel, M.; Ewert, S.; Abdullah, W.; Toygar, A.; Mudryi, V.; Al Badi, M.; Alzubdi, M.; Wilson, R.C.; Al Azkawi, H.S.; Ozdemir, H.N.; Abu, A.W.; Hertecant, J.; Razzaghy, A.M.; Funder, J.W.; Al Senani, A.; Sun, L.; Kim, S.M.; Yuen, T.; Zaidi, M.; New, M.I. Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency. Proc. Natl. Acad. Sci., 2017, 114(52), E11248-E11256.
[http://dx.doi.org/10.1073/pnas.1716621115] [PMID: 29229831]
[8]
Nimkarn, S.; New, M.I. Steroid 11β- hydroxylase deficiency congenital adrenal hyperplasia. Trends Endocrinol. Metab., 2008, 19(3), 96-99.
[http://dx.doi.org/10.1016/j.tem.2008.01.002] [PMID: 18294861]
[9]
Wei, C.; Zhang, Z.; Sang, M.; Dai, H.; Yang, T.; Sun, M. Compound heterozygosity of a novel Q73X mutation and a known R141X mutation in CYP11B1 resulting in 11β-hydroxylase deficiency in a Chinese boy with congenital adrenal hyperplasia. J. Steroid Biochem. Mol. Biol., 2021, 211, 105882.
[http://dx.doi.org/10.1016/j.jsbmb.2021.105882] [PMID: 33785438]
[10]
Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier, F.J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; Voelkerding, K.; Rehm, H.L. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet. Med., 2015, 17(5), 405-424.
[http://dx.doi.org/10.1038/gim.2015.30] [PMID: 25741868]
[11]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera? A visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[12]
Jumper, J.; Evans, R.; Pritzel, A.; Green, T.; Figurnov, M.; Ronneberger, O.; Tunyasuvunakool, K.; Bates, R.; Žídek, A.; Potapenko, A.; Bridgland, A.; Meyer, C.; Kohl, S.A.A.; Ballard, A.J.; Cowie, A.; Romera, P.B.; Nikolov, S.; Jain, R.; Adler, J.; Back, T.; Petersen, S.; Reiman, D.; Clancy, E.; Zielinski, M.; Steinegger, M.; Pacholska, M.; Berghammer, T.; Bodenstein, S.; Silver, D.; Vinyals, O.; Senior, A.W.; Kavukcuoglu, K.; Kohli, P.; Hassabis, D. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, 596(7873), 583-589.
[http://dx.doi.org/10.1038/s41586-021-03819-2] [PMID: 34265844]
[13]
Gidlöf, S.; Falhammar, H.; Thilén, A.; Von Döbeln, U.; Ritzén, M.; Wedell, A.; Nordenström, A. One hundred years of congenital adrenal hyperplasia in Sweden: A retrospective, population-based cohort study. Lancet Diabetes Endocrinol., 2013, 1(1), 35-42.
[http://dx.doi.org/10.1016/S2213-8587(13)70007-X] [PMID: 24622265]
[14]
Zachmann, M.; Tassinari, D.; Prader, A. Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 β-hydroxylase deficiency - A study of 25 patients. J. Clin. Endocrinol. Metab., 1983, 56(2), 222-229.
[http://dx.doi.org/10.1210/jcem-56-2-222] [PMID: 6296182]
[15]
Unluhizarci, K.; Kelestimur, F.; Güven, M.; Bayram, F.; Colak, R. The value of low dose (1 microg) ACTH stimulation test in the investigation of non-classic adrenal hyperplasia due to 11β-hydroxylase deficiency. Exp. Clin. Endocrinol. Diabetes, 2002, 110(8), 381-385.
[http://dx.doi.org/10.1055/s-2002-36422] [PMID: 12518247]
[16]
Kelestimur, F.; Şahin, Y.; Ayata, D.; Tutuş, A. The prevalence of nonclassic adrenal hyperplasia due to 11β-hydroxylase deficiency among hirsute women in a Turkish population. Clin. Endocrinol., 1996, 45(4), 381-384.
[http://dx.doi.org/10.1046/j.1365-2265.1996.8150825.x] [PMID: 8959074]
[17]
Oberman, A.S.; Flatau, E.; Luboshitzky, R. Bilateral testicular adrenal rests in a patient with 11-hydroxylase deficient congenital adrenal hyperplasia. J. Urol., 1993, 149(2), 350-352.
[http://dx.doi.org/10.1016/S0022-5347(17)36079-2] [PMID: 8426416]
[18]
Hochberg, Z.; Benderly, A.; Zadik, Z. Salt loss in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Arch. Dis. Child., 1984, 59(11), 1092-1094.
[http://dx.doi.org/10.1136/adc.59.11.1092] [PMID: 6334497]
[19]
Dundar, A.; Bayramov, R.; Onal, M.G.; Akkus, M.; Dogan, M.E.; Kenanoglu, S.; Cerrah, G.M.; Kazimli, U.; Ozbek, M.N.; Ercan, O.; Yildirim, R.; Celmeli, G.; Parlak, M.; Dundar, I.; Hatipoglu, N.; Unluhizarci, K.; Akalin, H.; Ozkul, Y.; Saatci, C.; Dundar, M. The molecular basis and genotype–phenotype correlations of Congenital Adrenal Hyperplasia (CAH) in Anatolian population. Mol. Biol. Rep., 2019, 46(4), 3677-3690.
[http://dx.doi.org/10.1007/s11033-019-04809-4] [PMID: 31006099]
[20]
Rösler, A.; Leiberman, E.; Cohen, T. High frequency of congenital adrenal hyperplasia (classic 11β-hydroxylase deficiency) among Jews from Morocco. Am. J. Med. Genet., 1992, 42(6), 827-834.
[http://dx.doi.org/10.1002/ajmg.1320420617] [PMID: 1554023]
[21]
Yildiz, M.; Isik, E.; Abali, Z.Y.; Keskin, M.; Ozbek, M.N.; Bas, F.; Ucakturk, S.A.; Buyukinan, M.; Onal, H.; Kara, C.; Storbeck, K.H.; Darendeliler, F.; Cayir, A.; Unal, E.; Anik, A.; Demirbilek, H.; Cetin, T.; Dursun, F.; Catli, G.; Turan, S.; Falhammar, H.; Baris, T.; Yaman, A.; Haklar, G.; Bereket, A.; Guran, T. Clinical and hormonal profiles correlate with molecular characteristics in patients with 11β-hydroxylase deficiency. J. Clin. Endocrinol. Metab., 2021, 106(9), e3714-e3724.
[http://dx.doi.org/10.1210/clinem/dgab225] [PMID: 33830237]
[22]
Yurekli, B.S.; Kutbay, N.O.; Onay, H.; Simsir, I.Y.; Kocabas, G.U.; Erdogan, M.; Cetinkalp, S.; Ozgen, G.; Saygili, F. A novel CYP11B1 mutation in a Turkish patient with 11β-hydroxylase deficiency: An association with the severe hypokalemia leading to rhabdomyolysis. Hormones, 2016, 15(2), 300-302.
[http://dx.doi.org/10.14310/horm.2002.1654] [PMID: 27376433]
[23]
Calissendorff, J.; Juhlin, C.C.; Sundin, A.; Bancos, I.; Falhammar, H. Adrenal myelolipomas. Lancet Diabetes Endocrinol., 2021, 9(11), 767-775.
[http://dx.doi.org/10.1016/S2213-8587(21)00178-9] [PMID: 34450092]

Rights & Permissions Print Cite
Article Metrics
35
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy