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Pathway Description
Segawa Syndrome
Homo sapiens
Disease Pathway
Created: 2013-08-29
Last Updated: 2022-11-01
Segawa syndrome is a condition in which the affected individual has a clumsy or unusual gait, and experiences involuntary muscle contractions and uncontrolled movements (dystonia). Some cases are mild, while others can be severe. The beginning signs of this condition are dystonia in the legs, and clubfeet. The cause of this condition is a mutation in the GCH1 gene. Tetrahydrobiopterin is an important compound in the production of neurotransmitters, specifically dopamine and serotonin, and the processing of quite a few amino acids, The mutation on GCH1 causes GTP cyclohydrase 1 production to be reduced or absent which causes the first three steps of tetrahydrobiopterin biosynthesis to be compromised. Dopamine is imperative in maintaining smooth muscle movements, which is why patients with Segawa syndrome experience movement problems and an unusual gait.
References
Segawa Syndrome References
[Metagen: SEGAWA SYNDROME](http://metagene.de/program/d.prg?id_d=391)
[OMIM: 128230](http://omim.org/entry/128230})
Segawa M, Hosaka A, Miyagawa F, Nomura Y, Imai H: Hereditary progressive dystonia with marked diurnal fluctuation. Adv Neurol. 1976;14:215-33.
Pubmed: 945938
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Pubmed: 10585338
Pterine Biosynthesis References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
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Pubmed: 10727395
Longo N: Disorders of biopterin metabolism. J Inherit Metab Dis. 2009 Jun;32(3):333-42. doi: 10.1007/s10545-009-1067-2. Epub 2009 Feb 9.
Pubmed: 19234759
Crabtree MJ, Channon KM: Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease. Nitric Oxide. 2011 Aug 1;25(2):81-8. doi: 10.1016/j.niox.2011.04.004. Epub 2011 Apr 22.
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Duan CL, Su Y, Zhao CL, Lu LL, Xu QY, Yang H: The assays of activities and function of TH, AADC, and GCH1 and their potential use in ex vivo gene therapy of PD. Brain Res Brain Res Protoc. 2005 Dec;16(1-3):37-43. doi: 10.1016/j.brainresprot.2005.10.005.
Pubmed: 16338639
Togari A, Ichinose H, Matsumoto S, Fujita K, Nagatsu T: Multiple mRNA forms of human GTP cyclohydrolase I. Biochem Biophys Res Commun. 1992 Aug 31;187(1):359-65. doi: 10.1016/s0006-291x(05)81501-3.
Pubmed: 1520321
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Pubmed: 14702039
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Pubmed: 16572171
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Pubmed: 15489334
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Pubmed: 1282802
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Pubmed: 8216273
Ashida A, Owada M, Hatakeyama K: A missense mutation (A to G) of 6-pyruvoyltetrahydropterin synthase in tetrahydrobiopterin-deficient form of hyperphenylalaninemia. Genomics. 1994 Nov 15;24(2):408-10. doi: 10.1006/geno.1994.1642.
Pubmed: 7698774
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