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Gene Review

ALDH5A1  -  aldehyde dehydrogenase 5 family, member A1

Homo sapiens

Synonyms: Aldehyde dehydrogenase family 5 member A1, NAD(+)-dependent succinic semialdehyde dehydrogenase, SSADH, SSDH, Succinate-semialdehyde dehydrogenase, mitochondrial
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Disease relevance of ALDH5A1


Psychiatry related information on ALDH5A1


High impact information on ALDH5A1


Chemical compound and disease context of ALDH5A1


Biological context of ALDH5A1


Anatomical context of ALDH5A1


Associations of ALDH5A1 with chemical compounds

  • Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency [15].
  • Mammalian SSADH contains significant homology to bacterial NADP(+)-succinic semialdehyde dehydrogenase (EC and conserved regions of general aldehyde dehydrogenases (EC, suggesting it is a member of the aldehyde dehydrogenase superfamily of proteins [16].
  • In human, SSADH deficiency results in 4-hydroxybutyric aciduria, an autosomal recessive disorder due to an accumulation of GABA and 4-hydroxybutyric acid in the CNS [17].
  • Compared to the other defects of GABA degradation, succinic semialdehyde dehydrogenase (SSADH, EC deficiency with > 150 patients (McKusick 271980) and pyridoxine-dependent seizures with > 100 patients ('putative' glutamic acid decarboxylase (GAD, EC deficiency; McKusick 266100), GABA-T deficiency is very rare [22].
  • Therapeutic intervention for human succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) has been limited to vigabatrin (VGB) [23].

Other interactions of ALDH5A1

  • In summary, we report the first patient with the exceptional rare findings of both SSADH deficiency and partial WAGR/WAGRO syndrome [24].
  • Candidate gene analysis of the succinic semialdehyde dehydrogenase gene (ALDH5A1) in patients with idiopathic generalized epilepsy and photosensitivity [1].
  • Mutation screening of the ALDH5A1 coding sequence of 35IGE/PPR patients and four healthy control subjects identified 17 sequence variants, of which three resulted in an exchange of amino acids (H180Y, P182L, A237S) [1].
  • Association analysis was carried out for six single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (TNR, intron 1), covering the genomic ALDH5A1 sequence [1].
  • The large cluster has additionally been covered by a sequence ready PAC contig and three probably unrelated genes (TRMI2, BTN and SSADH) have been accurately localized within the 6p22.2-p22.1 region [25].

Analytical, diagnostic and therapeutic context of ALDH5A1

  • After extracting mRNA and genomic DNA from his cultured lymphoblasts, we analyzed the entire coding region of the ALDH5A1 gene using reverse transcription-polymerase chain reaction (RT-PCR) and genomic PCR followed by sequencing [14].
  • Northern blot analysis revealed two differentially expressed SSADH transcripts of approximately 2.0 and 6.0 kilobases in both rat and human tissues [16].
  • Sequence analysis of SSADH revealed four changes affecting the encoded protein, only one of which had a minor allele whose frequency is even moderately common [5].
  • The present results do not provide evidence that any ALDH5A1 missense variant itself contributes a common and substantial susceptibility effect (RR>2) to IGE syndromes or an increased liability to visually-induced cortical synchronization [1].
  • We conclude that vigabatrin in SSADH deficiency should be administered in a gradually increasing dosage combined with frequent evaluation of the clinical condition and the EEG [4].


  1. Candidate gene analysis of the succinic semialdehyde dehydrogenase gene (ALDH5A1) in patients with idiopathic generalized epilepsy and photosensitivity. Lorenz, S., Heils, A., Taylor, K.P., Gehrmann, A., Muhle, H., Gresch, M., Becker, T., Tauer, U., Stephani, U., Sander, T. Neurosci. Lett. (2006) [Pubmed]
  2. Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. Gropman, A. Ann. Neurol. (2003) [Pubmed]
  3. Clinical aspects of the disorders of GABA metabolism in children. Pearl, P.L., Gibson, K.M. Curr. Opin. Neurol. (2004) [Pubmed]
  4. Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (gamma-vinyl-GABA). Matern, D., Lehnert, W., Gibson, K.M., Korinthenberg, R. J. Inherit. Metab. Dis. (1996) [Pubmed]
  5. A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability. Plomin, R., Turic, D.M., Hill, L., Turic, D.E., Stephens, M., Williams, J., Owen, M.J., O'Donovan, M.C. Mol. Psychiatry (2004) [Pubmed]
  6. The molecular basis of succinic semialdehyde dehydrogenase deficiency in one family. Bekri, S., Fossoud, C., Plaza, G., Guenne, A., Salomons, G.S., Jakobs, C., Van Obberghen, E. Mol. Genet. Metab. (2004) [Pubmed]
  7. Inherited disorders of neurotransmitters in children and adults. Pearl, P.L., Capp, P.K., Novotny, E.J., Gibson, K.M. Clin. Biochem. (2005) [Pubmed]
  8. Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase. Hogema, B.M., Gupta, M., Senephansiri, H., Burlingame, T.G., Taylor, M., Jakobs, C., Schutgens, R.B., Froestl, W., Snead, O.C., Diaz-Arrastia, R., Bottiglieri, T., Grompe, M., Gibson, K.M. Nat. Genet. (2001) [Pubmed]
  9. Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). Chambliss, K.L., Hinson, D.D., Trettel, F., Malaspina, P., Novelletto, A., Jakobs, C., Gibson, K.M. Am. J. Hum. Genet. (1998) [Pubmed]
  10. Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAA receptor-mediated mechanisms. Wu, Y., Buzzi, A., Frantseva, M., Velazquez, J.P., Cortez, M., Liu, C., Shen, L., Gibson, K.M., Snead, O.C. Ann. Neurol. (2006) [Pubmed]
  11. Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. Gupta, M., Jansen, E.E., Senephansiri, H., Jakobs, C., Snead, O.C., Grompe, M., Gibson, K.M. Mol. Ther. (2004) [Pubmed]
  12. Gamma-hydroxybutyric aciduria: a biochemist's education from a heritable disorder of GABA metabolism. Gibson, K.M. J. Inherit. Metab. Dis. (2005) [Pubmed]
  13. Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. Cortez, M.A., Wu, Y., Gibson, K.M., Snead, O.C. Pharmacol. Biochem. Behav. (2004) [Pubmed]
  14. Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T > A of the ALDH5A1 gene. Aoshima, T., Kajita, M., Sekido, Y., Ishiguro, Y., Tsuge, I., Kimura, M., Yamaguchi, S., Watanabe, K., Shimokata, K., Niwa, T. Hum. Hered. (2002) [Pubmed]
  15. Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. Akaboshi, S., Hogema, B.M., Novelletto, A., Malaspina, P., Salomons, G.S., Maropoulos, G.D., Jakobs, C., Grompe, M., Gibson, K.M. Hum. Mutat. (2003) [Pubmed]
  16. Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde dehydrogenase from rat and human. cDNA isolation, evolutionary homology, and tissue expression. Chambliss, K.L., Caudle, D.L., Hinson, D.D., Moomaw, C.R., Slaughter, C.A., Jakobs, C., Gibson, K.M. J. Biol. Chem. (1995) [Pubmed]
  17. Structure of human succinic semialdehyde dehydrogenase gene: identification of promoter region and alternatively processed isoforms. Blasi, P., Boyl, P.P., Ledda, M., Novelletto, A., Gibson, K.M., Jakobs, C., Hogema, B., Akaboshi, S., Loreni, F., Malaspina, P. Mol. Genet. Metab. (2002) [Pubmed]
  18. Gastrodin decreases immunoreactivities of gamma-aminobutyric acid shunt enzymes in the hippocampus of seizure-sensitive gerbils. An, S.J., Park, S.K., Hwang, I.K., Choi, S.Y., Kim, S.K., Kwon, O.S., Jung, S.J., Baek, N.I., Lee, H.Y., Won, M.H., Kang, T.C. J. Neurosci. Res. (2003) [Pubmed]
  19. gamma-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues. Tillakaratne, N.J., Medina-Kauwe, L., Gibson, K.M. Comp. Biochem. Physiol. A Physiol. (1995) [Pubmed]
  20. Monitoring of 4-hydroxybutyric acid levels in body fluids during vigabatrin treatment in succinic semialdehyde dehydrogenase deficiency. Ergezinger, K., Jeschke, R., Frauendienst-Egger, G., Korall, H., Gibson, K.M., Schuster, V.H. Ann. Neurol. (2003) [Pubmed]
  21. Spatial and temporal alterations in the GABA shunt in the gerbil hippocampus following transient ischemia. Kang, T.C., Park, S.K., Hwang, I.K., An, S.J., Choi, S.Y., Cho, S.W., Won, M.H. Brain Res. (2002) [Pubmed]
  22. 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. Medina-Kauwe, L.K., Tobin, A.J., De Meirleir, L., Jaeken, J., Jakobs, C., Nyhan, W.L., Gibson, K.M. J. Inherit. Metab. Dis. (1999) [Pubmed]
  23. Therapeutic intervention in mice deficient for succinate semialdehyde dehydrogenase (gamma-hydroxybutyric aciduria). Gupta, M., Greven, R., Jansen, E.E., Jakobs, C., Hogema, B.M., Froestl, W., Snead, O.C., Bartels, H., Grompe, M., Gibson, K.M. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  24. Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity. Jung, R., Rauch, A., Salomons, G.S., Verhoeven, N.M., Jakobs, C., Michael Gibson, K., Lachmann, E., Sass, J.O., Trautmann, U., Zweier, C., Staatz, G., Knerr, I. Mol. Genet. Metab. (2006) [Pubmed]
  25. Physical mapping of two histone gene clusters on human chromosome 6p22.1-22.2. Volz, A., Albig, W., Doenecke, D., Ziegler, A. DNA Seq. (1997) [Pubmed]
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