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Pathway Description
DOPA-Responsive Dystonia
Homo sapiens
Disease Pathway
DOPA-Responsive Dystonia is a condition in which the muscles contract, experience tremors 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 usually a mutation in the GCH1 gene, but can sometimes be attributed to mutations in the TH or SPR genes. 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 production to be reduced or absent which causes the first three steps of tetrahydrobiopterin biosynthesis to be compromised. The mutation on the SPR gene affects tetrahydrobiopterin biosynthesis by interfering with the production of sepiapterin reductase, which is needed to complete the final step of tetrahydrobiopterin biosynthesis. The TH gene mutation also affects dopamine production through the decreased function of an enzyme called tyrosine hydroxylase, which is responsible for converting tyrosine to dopamine. Dopamine is imperative in maintaining smooth muscle movements, which is why patients with DOPA-responive dystonia experience tremors and movement problems.
References
DOPA-Responsive Dystonia References
[Metagen: DOPA-RESPONSIVE DYSTONIA](http://metagene.de/program/d.prg?id_d=451)
[OMIM: 600225](http://omim.org/entry/600225})
[NIH](http://ghr.nlm.nih.gov/condition/dopa-responsive-dystonia)
Wijemanne S, Jankovic J: Dopa-responsive dystonia--clinical and genetic heterogeneity. Nat Rev Neurol. 2015 Jul;11(7):414-24. doi: 10.1038/nrneurol.2015.86. Epub 2015 Jun 23.
Pubmed: 26100751
Rose SJ, Yu XY, Heinzer AK, Harrast P, Fan X, Raike RS, Thompson VB, Pare JF, Weinshenker D, Smith Y, Jinnah HA, Hess EJ: A new knock-in mouse model of l-DOPA-responsive dystonia. Brain. 2015 Oct;138(Pt 10):2987-3002. doi: 10.1093/brain/awv212. Epub 2015 Jul 27.
Pubmed: 26220941
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.
Thony B, Auerbach G, Blau N: Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J. 2000 Apr 1;347 Pt 1:1-16.
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.
Pubmed: 21550412
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