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Pathway Description
Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia Due to 17 alpha-Hydroxylase Deficiency
Homo sapiens
Disease Pathway
Adrenal hyperplasia type 5 (AH5) also known as Congenital Adrenal Hyperplasia Due to 17 alpha-Hydroxylase Deficiency is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of cortisol and sex steroids synthesis caused by a defect in the CYP17A1 gene which codes for Steroid 17-alpha-hydroxylase/17,20 lyase. These 2 enzymes catalyze pregnenolone and progesterone to their 17-hydroxy forms in steroidogenesis and mediate three key transformations in cortisol and sex steroid synthesis. This disorder is characterized by a decrease in both cortisol and sex steroids and increase in mineralocorticoids. Symptoms of the disorder include mild hypocortisolism, ambiguous genitalia in genetic males or failure of the ovaries to function at puberty in genetic females, and hypertension. Treatments for Hypertension and mineralocorticoid excess is done with glucocorticoid replacement. Genetically female patients need female hormone replacement to induce puberty and regulate menses. Surgery may be needed for males with ambiguous genitalia. Testosterone must be replaced for genetically males (XY) to induce puberty and continued throughout adult life. It is estimated that Adrenal hyperplasia type 5 affects 1 in 1 million individuals worldwide.
References
Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia Due to 17 alpha-Hydroxylase Deficiency References
[Wikipedia: Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency](http://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_17_alpha-hydroxylase_deficiency)
[Uniprot: P05093](http://www.uniprot.org/uniprot/P05093)
[eMedicine: Article 920532-overview](http://emedicine.medscape.com/article/920532-overview)
[OMIM](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=202110)
Biglieri EG: 17 alpha-Hydroxylase deficiency: 1963-1966. J Clin Endocrinol Metab. 1997 Jan;82(1):48-50. doi: 10.1210/jcem.82.1.3653.
Pubmed: 8989231
Biglieri EG, Herron MA, Brust N: 17-hydroxylation deficiency in man. J Clin Invest. 1966 Dec;45(12):1946-54. doi: 10.1172/JCI105499.
Pubmed: 4288776
Geller DH, Auchus RJ, Mendonca BB, Miller WL: The genetic and functional basis of isolated 17,20-lyase deficiency. Nat Genet. 1997 Oct;17(2):201-5. doi: 10.1038/ng1097-201.
Pubmed: 9326943
Heremans GF, Moolenaar AJ, van Gelderen HH: Female phenotype in a male child due to 17-alpha-hydroxylase deficiency. Arch Dis Child. 1976 Sep;51(9):721-3.
Pubmed: 999330
Kumar N: Congenital adrenal hyperplasia due to 17-alpha hydroxylase deficiency with hypertensive encephalopathy, hypoglycemic seizures and adrenal insufficiency. J Anaesthesiol Clin Pharmacol. 2018 Apr-Jun;34(2):261-262. doi: 10.4103/0970-9185.173401.
Pubmed: 30104848
Steroidogenesis References
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.
Pubmed: 23770321
George FW, Russell DW, Wilson JD: Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8044-7. doi: 10.1073/pnas.88.18.8044.
Pubmed: 1654556
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.
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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