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Pathway Description
Hyperphenylalaninemia Due to Guanosine Triphosphate Cyclohydrolase Deficiency
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2022-10-25
Last Updated: 2023-10-25
Hyperphenylalaninemia is the high presence of phenylalanine in the system/blood caused by a genetic mutation. In this case a missense error in the gene which encodes GTP cyclohydrolase. Consequently, this form of hyperphenylalaninemia is also called GTP cyclohydrolase I deficiency and/or dopa-responsive dystonia. It is an autosomal recessive mutation. The mutation results in a reduction in the production of BH4 which is a necessary component in the reaction which transforms phenylalanine to other products in the body. Common symptoms include: abnormality of eye mpvement, choreoathetosis, dysphagia, dystonia, excessive salivation, hyperkinesis, lethargy, limb hyptertonia, seizures, tremor, among others.
References
Hyperphenylalaninemia Due to Guanosine Triphosphate Cyclohydrolase Deficiency References
Hwu WL, Wang PJ, Hsiao KJ, Wang TR, Chiou YW, Lee YM: Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase I mutation. Hum Genet. 1999 Sep;105(3):226-30. doi: 10.1007/s004390051093.
Pubmed: 10987649
Blau N, Ichinose H, Nagatsu T, Heizmann CW, Zacchello F, Burlina AB: A missense mutation in a patient with guanosine triphosphate cyclohydrolase I deficiency missed in the newborn screening program. J Pediatr. 1995 Mar;126(3):401-5. doi: 10.1016/s0022-3476(95)70458-2.
Pubmed: 7869202
Coskun T, Karagoz T, Kalkanoglu S, Tokatli A, Ozalp I, Thony B, Blau N: Guanosine triphosphate cyclohydrolase I deficiency: a rare cause of hyperphenylalaninemia. Turk J Pediatr. 1999 Apr-Jun;41(2):231-7.
Pubmed: 10770663
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
Gutlich M, Jaeger E, Rucknagel KP, Werner T, Rodl W, Ziegler I, Bacher A: Human GTP cyclohydrolase I: only one out of three cDNA isoforms gives rise to the active enzyme. Biochem J. 1994 Aug 15;302 ( Pt 1):215-21. doi: 10.1042/bj3020215.
Pubmed: 8068008
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Pubmed: 14702039
Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. doi: 10.1038/nature04601.
Pubmed: 16572171
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Pubmed: 15489334
Thony B, Leimbacher W, Burgisser D, Heizmann CW: Human 6-pyruvoyltetrahydropterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme. Biochem Biophys Res Commun. 1992 Dec 30;189(3):1437-43. doi: 10.1016/0006-291x(92)90235-d.
Pubmed: 1282802
Ashida A, Hatakeyama K, Kagamiyama H: cDNA cloning, expression in Escherichia coli and purification of human 6-pyruvoyl-tetrahydropterin synthase. Biochem Biophys Res Commun. 1993 Sep 30;195(3):1386-93. doi: 10.1006/bbrc.1993.2197.
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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