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Pathway Description
Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Homo sapiens
Disease Pathway
Adrenal hyperplasia type 3, also called Congenital adrenal hyperplasia due to 21-hydroxylase deficiency, is caused by a defect in the CYP21A2 gene which codes for Steroid 21-hydroxylase (21-hydroxylase). Steroid 21-hydroxylase catalyzes hydroxylation of 17-hydroxyprogesterone to 11-deoxycortisol in the glucocorticoid pathway from pregnenolone to cortisol. It also catalyzes hydroxylation of progesterone to 11-deoxycorticosterone (DOC) in the mineralocorticoid pathway on its way from pregnenolone to aldosterone. A defect in this enzyme results in accumulation of 17-Hydroxyprogesterone, progesterone and 17a-Hydroxypregnenolone, androstenedione, and testosterone; decreased levels of cortexolone, deoxycorticosterone, aldosterone and cortisol. Symptoms include salt-wasting crises in infancy due to the lack of aldosterone, like spitting, poor weight gain, vomiting, severe dehydration, and circulatory collapse. The high level of testosterone results in virilization and genital ambiguity of female infants.
References
Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency References
de-Araujo M, Sanches MR, Suzuki LA, Guerra G Jr, Farah SB, de-Mello MP: Molecular analysis of CYP21 and C4 genes in Brazilian families with the classical form of steroid 21-hydroxylase deficiency. Braz J Med Biol Res. 1996 Jan;29(1):1-13.
Pubmed: 8731325
Araujo RS, Mendonca BB, Barbosa AS, Lin CJ, Marcondes JA, Billerbeck AE, Bachega TA: Microconversion between CYP21A2 and CYP21A1P promoter regions causes the nonclassical form of 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2007 Oct;92(10):4028-34. doi: 10.1210/jc.2006-2163. Epub 2007 Jul 31.
Pubmed: 17666484
Bachega TA, Billerbeck AE, Madureira G, Marcondes JA, Longui CA, Leite MV, Arnhold IJ, Mendonca BB: Molecular genotyping in Brazilian patients with the classical and nonclassical forms of 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1998 Dec;83(12):4416-9. doi: 10.1210/jcem.83.12.5350.
Pubmed: 9851787
Charmandari E, Hindmarsh PC, Johnston A, Brook CG: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: alterations in cortisol pharmacokinetics at puberty. J Clin Endocrinol Metab. 2001 Jun;86(6):2701-8. doi: 10.1210/jcem.86.6.7522.
Pubmed: 11397874
White PC, Bachega TA: Congenital adrenal hyperplasia due to 21 hydroxylase deficiency: from birth to adulthood. Semin Reprod Med. 2012 Oct;30(5):400-9. doi: 10.1055/s-0032-1324724. Epub 2012 Oct 8.
Pubmed: 23044877
https://www.omim.org/entry/201910
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Norman, A.W, and Litwack, G. Hormones (2nd ed.) (1997) San Diego : Academic Press.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Miller WL: Molecular biology of steroid hormone synthesis. Endocr Rev. 1988 Aug;9(3):295-318. doi: 10.1210/edrv-9-3-295.
Pubmed: 3061784
HECHTER O, SOLOMON MM, ZAFFARONI A, PINCUS G: Transformation of cholesterol and acetate to adrenal cortical hormones. Arch Biochem Biophys. 1953 Sep;46(1):201-14. doi: 10.1016/0003-9861(53)90182-9.
Pubmed: 13092959
Luu-The V: Assessment of steroidogenesis and steroidogenic enzyme functions. J Steroid Biochem Mol Biol. 2013 Sep;137:176-82. doi: 10.1016/j.jsbmb.2013.05.017. Epub 2013 Jun 13.
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Andersson S, Berman DM, Jenkins EP, Russell DW: Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature. 1991 Nov 14;354(6349):159-61. doi: 10.1038/354159a0.
Pubmed: 1944596
Emanuelsson I, Almokhtar M, Wikvall K, Gronbladh A, Nylander E, Svensson AL, Fex Svenningsen A, Norlin M: Expression and regulation of CYP17A1 and 3beta-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis. Neurochem Int. 2018 Feb;113:46-55. doi: 10.1016/j.neuint.2017.11.007. Epub 2017 Nov 21.
Pubmed: 29162485
Kimoto T, Asou H, Ohta Y, Mukai H, Chernogolov AA, Kawato S: Digital fluorescence imaging of elementary steps of neurosteroid synthesis in rat brain glial cells. J Pharm Biomed Anal. 1997 Jun;15(9-10):1231-40. doi: 10.1016/s0731-7085(96)01987-5.
Pubmed: 9226548
Verschoor-Klootwyk AH, Verschoor L, Azhar S, Reaven GM: Role of exogenous cholesterol in regulation of adrenal steroidogenesis in the rat. J Biol Chem. 1982 Jul 10;257(13):7666-71.
Pubmed: 6282849
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