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Pathway Description
4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency
Homo sapiens
Disease Pathway
Created: 2013-08-01
Last Updated: 2022-12-14
4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency (SSADH; Gamma-hydroxybutyric acidemia) inhibits the formation of succinate from GABA. This deficiency results in urinary excretion of 4-hydroxybutyric acid. In vivo proton MR also indicates elevated GABA levels as compared with an age-matched control. Symptoms include ataxia, chorea or athetosis, motor retardation, seizures, macrocephaly and delayed or abnormal speech development.
References
4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency References
[OMIM: Entry 271980](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=271980)
[Uniprot: P51649](http://www.uniprot.org/uniprot/P51649)
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Akaboshi S, Hogema BM, Novelletto A, Malaspina P, Salomons GS, Maropoulos GD, Jakobs C, Grompe M, Gibson KM: Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. Hum Mutat. 2003 Dec;22(6):442-50. doi: 10.1002/humu.10288.
Pubmed: 14635103
Blasi P, Palmerio F, Caldarola S, Rizzo C, Carrozzo R, Gibson KM, Novelletto A, Deodato F, Cappa M, Dioni-Vici C, Malaspina P: Succinic semialdehyde dehydrogenase deficiency: clinical, biochemical and molecular characterization of a new patient with severe phenotype and a novel mutation. Clin Genet. 2006 Mar;69(3):294-6. doi: 10.1111/j.1399-0004.2006.00579.x.
Pubmed: 16542398
Gibson KM, Christensen E, Jakobs C, Fowler B, Clarke MA, Hammersen G, Raab K, Kobori J, Moosa A, Vollmer B, Rossier E, Iafolla AK, Matern D, Brouwer OF, Finkelstein J, Aksu F, Weber HP, Bakkeren JA, Gabreels FJ, Bluestone D, Barron TF, Beauvais P, Rabier D, Santos C, Lehnert W, et al.: The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients. Pediatrics. 1997 Apr;99(4):567-74.
Pubmed: 9093300
Gibson KM, Hoffmann GF, Hodson AK, Bottiglieri T, Jakobs C: 4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism. Neuropediatrics. 1998 Feb;29(1):14-22. doi: 10.1055/s-2007-973527.
Pubmed: 9553943
Gibson KM, Sweetman L, Nyhan WL, Jakobs C, Rating D, Siemes H, Hanefeld F: Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. Clin Chim Acta. 1983 Sep 15;133(1):33-42.
Pubmed: 6627675
Hogema BM, Gupta M, Senephansiri H, Burlingame TG, Taylor M, Jakobs C, Schutgens RB, Froestl W, Snead OC, Diaz-Arrastia R, Bottiglieri T, Grompe M, Gibson KM: Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase. Nat Genet. 2001 Oct;29(2):212-6. doi: 10.1038/ng727.
Pubmed: 11544478
Glutamate Metabolism References
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Pubmed: 11181995
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Pubmed: 14702039
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Pubmed: 12444921
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Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. doi: 10.1038/nature03466.
Pubmed: 15815621
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