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Pathway Description
Aromatic L-Aminoacid Decarboxylase Deficiency
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2013-08-01
Last Updated: 2022-11-02
Aromatic L-Aminoacid Decarboxylase Deficiency (DOPA decarboxylase; DDC) is an autosomal recessive disease caused by a mutation in the DDC gene which codes for aromatic-L-aminoacid decarboxylase. A deficiency in this enzyme results in accumulation of 3-methoxytyrosine, 5-hydroxy-L-tryptophan, and L-Dopa in plasma, spinal fluid, and urine; 3-methoxytyramine and dopamine in urine. It also results in decreased concentrations of homovanillic acid, S-adenosylmethionine, and 5-hydroxytryptophol in spinal fluid; and epinephrine, norepinephrine in plasma. Symptoms include temperature instability, hypotonia, mental and motor retardation, and cerebral atrophy.
References
Aromatic L-Aminoacid Decarboxylase Deficiency References
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.22 Heilbronn: SPS Verlagsgesellschaft
[Uniprot: P20711](http://www.uniprot.org/uniprot/P20711)
[OMIM: Entry 608643](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608643)
Verbeek MM, Geurtz PB, Willemsen MA, Wevers RA: Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes. Mol Genet Metab. 2007 Apr;90(4):363-9. doi: 10.1016/j.ymgme.2006.12.001. Epub 2007 Jan 19.
Pubmed: 17240182
Swoboda KJ, Saul JP, McKenna CE, Speller NB, Hyland K: Aromatic L-amino acid decarboxylase deficiency: overview of clinical features and outcomes. Ann Neurol. 2003;54 Suppl 6:S49-55. doi: 10.1002/ana.10631.
Pubmed: 12891654
Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC: Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis. Neurology. 2004 Apr 13;62(7):1058-65.
Pubmed: 15079002
Brun L, Ngu LH, Keng WT, Ch'ng GS, Choy YS, Hwu WL, Lee WT, Willemsen MA, Verbeek MM, Wassenberg T, Regal L, Orcesi S, Tonduti D, Accorsi P, Testard H, Abdenur JE, Tay S, Allen GF, Heales S, Kern I, Kato M, Burlina A, Manegold C, Hoffmann GF, Blau N: Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology. 2010 Jul 6;75(1):64-71. doi: 10.1212/WNL.0b013e3181e620ae. Epub 2010 May 26.
Pubmed: 20505134
Lee NC, Shieh YD, Chien YH, Tzen KY, Yu IS, Chen PW, Hu MH, Hu MK, Muramatsu S, Ichinose H, Hwu WL: Regulation of the dopaminergic system in a murine model of aromatic L-amino acid decarboxylase deficiency. Neurobiol Dis. 2013 Apr;52:177-90. doi: 10.1016/j.nbd.2012.12.005. Epub 2012 Dec 26.
Pubmed: 23275025
Catecholamine 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.
Starke K: History of catecholamine research. Chem Immunol Allergy. 2014;100:288-301. doi: 10.1159/000359962. Epub 2014 May 23.
Pubmed: 24925409
Kaneda N, Kobayashi K, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. Biochem Biophys Res Commun. 1987 Aug 14;146(3):971-5. doi: 10.1016/0006-291x(87)90742-x.
Pubmed: 2887169
Grima B, Lamouroux A, Boni C, Julien JF, Javoy-Agid F, Mallet J: A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Nature. 1987 Apr 16-22;326(6114):707-11. doi: 10.1038/326707a0.
Pubmed: 2882428
Kobayashi K, Kaneda N, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3. Nucleic Acids Res. 1987 Aug 25;15(16):6733. doi: 10.1093/nar/15.16.6733.
Pubmed: 2888085
Ichinose H, Kurosawa Y, Titani K, Fujita K, Nagatsu T: Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1024-30. doi: 10.1016/0006-291x(89)91772-5.
Pubmed: 2590185
Scherer LJ, McPherson JD, Wasmuth JJ, Marsh JL: Human dopa decarboxylase: localization to human chromosome 7p11 and characterization of hepatic cDNAs. Genomics. 1992 Jun;13(2):469-71.
Pubmed: 1612608
Sumi-Ichinose C, Ichinose H, Takahashi E, Hori T, Nagatsu T: Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis. Biochemistry. 1992 Mar 3;31(8):2229-38. doi: 10.1021/bi00123a004.
Pubmed: 1540578
Williams HJ, Bray N, Murphy KC, Cardno AG, Jones LA, Owen MJ: No evidence for allelic association between schizophrenia and a functional variant of the human dopamine beta-hydroxylase gene (DBH). Am J Med Genet. 1999 Oct 15;88(5):557-9.
Pubmed: 10490716
Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. doi: 10.1038/nature02465.
Pubmed: 15164053
Lamouroux A, Vigny A, Faucon Biguet N, Darmon MC, Franck R, Henry JP, Mallet J: The primary structure of human dopamine-beta-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme. EMBO J. 1987 Dec 20;6(13):3931-7.
Pubmed: 3443096
Kaneda N, Ichinose H, Kobayashi K, Oka K, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis. J Biol Chem. 1988 Jun 5;263(16):7672-7.
Pubmed: 3372503
Baetge EE, Behringer RR, Messing A, Brinster RL, Palmiter RD: Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina. Proc Natl Acad Sci U S A. 1988 May;85(10):3648-52. doi: 10.1073/pnas.85.10.3648.
Pubmed: 2835776
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
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