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Pathway Description
Hyperphenylalaninemia Due to DHPR-Deficiency
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-16
Hyperphenylalaninemia due to dihydropteridine reductase deficiency (DHPR) is the high presence of phenylalanine in the system/blood caused by a genetic mutation. More specificially, mutations in the QDPR gene are the root cause of the condition. One observes that such a mutation results in an error encoding a reductase enzyme, and from there a chain reaction of effects lead to the observed effects of the disease. The mutation is autosomal recessive.
When tetrahydrobiopterin levels drop, the breakdown of many several amino acids, such as phenylalanine, is reduced and as a result their levels in the blood augment.
Symptoms of hyperphenylalaninemia due to dihydropteridine reductase deficiency include: dysphagia, global development delay, microcephaly, and intellectual disability (among others). Treatment consists of BH4 supplements as well as other medical treatments.
References
Hyperphenylalaninemia Due to DHPR-Deficiency References
Arai N, Narisawa K, Hayakawa H, Tada K: Hyperphenylalaninemia due to dihydropteridine reductase deficiency: diagnosis by enzyme assays on dried blood spots. Pediatrics. 1982 Sep;70(3):426-30.
Pubmed: 7110817
Pterine Biosynthesis References
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Pubmed: 10727395
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Pubmed: 8304101
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Pubmed: 16141072
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
Pubmed: 21183079
Turri MO, Ilg EC, Thony B, Blau N: Structure, genomic localization and recombinant expression of the mouse 6-pyruvoyl-tetrahydropterin synthase gene. Biol Chem. 1998 Dec;379(12):1441-7.
Pubmed: 9894812
Ota A, Ichinose H, Nagatsu T: Mouse sepiapterin reductase: an enzyme involved in the final step of tetrahydrobiopterin biosynthesis. Primary structure deduced from the cDNA sequence. Biochim Biophys Acta. 1995 Feb 21;1260(3):320-2. doi: 10.1016/0167-4781(94)00225-r.
Pubmed: 7873607
Lee SW, Park IY, Hahn Y, Lee JE, Seong CS, Chung JH, Park YS: Cloning of mouse sepiapterin reductase gene and characterization of its promoter region. Biochim Biophys Acta. 1999 Apr 14;1445(1):165-71. doi: 10.1016/s0167-4781(99)00030-5.
Pubmed: 10209270
Maier J, Schott K, Werner T, Bacher A, Ziegler I: Northern blot analysis of sepiapterin reductase mRNA in mammalian cell lines and tissues. Adv Exp Med Biol. 1993;338:195-8. doi: 10.1007/978-1-4615-2960-6_39.
Pubmed: 8304109
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000489
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