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Normal Function
The ALDH5A1 gene provides instructions for producing the succinic semialdehyde dehydrogenase enzyme. This enzyme is found in the energy-producing centers of cells (mitochondria). Succinic semialdehyde dehydrogenase is involved in the breakdown of a chemical that transmits signals in the brain (neurotransmitter) called gamma-amino butyric acid (GABA). The primary role of GABA is to prevent the brain from being overloaded with too many signals. Once GABA molecules have been released from nerve cells, they are broken down by succinic semialdehyde dehydrogenase and other enzymes.
Health Conditions Related to Genetic Changes
Succinic semialdehyde dehydrogenase deficiency
Variants (also called mutations) in the ALDH5A1 gene have been found to cause succinic semialdehyde dehydrogenase deficiency. This is a disorder that can cause a variety of neurological problems. Most of the variants that cause this condition lead to the production of an enzyme with little or no activity. A lack of functional succinic semialdehyde dehydrogenase disrupts the conversion of succinic semialdehyde to succinic acid. Instead, succinic semialdehyde is converted back into GABA or a related molecule, gamma-hydroxybutyrate (GHB). It is unclear how increases in GHB and GABA cause developmental delays, seizures, and other features of succinic semialdehyde dehydrogenase deficiency.
Research has shown that people with ALDH5A1 gene variants that result in a lack of functional succinic semialdehyde dehydrogenase tend to have more severe signs and symptoms than people who have gene variants that impair protein activity.
More About This Health ConditionOther Names for This Gene
- aldehyde dehydrogenase 5 family, member A1
- aldehyde dehydrogenase 5 family, member A1 (succinate-semialdehyde dehydrogenase)
- aldehyde dehydrogenase 5A1
- mitochondrial succinate semialdehyde dehydrogenase
- NAD(+)-dependent succinic semialdehyde dehydrogenase
- SSADH
- SSDH
- SSDH_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- 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. Citation on PubMed
- Blasi P, Boyl PP, Ledda M, Novelletto A, Gibson KM, Jakobs C, Hogema B, Akaboshi S, Loreni F, Malaspina P. Structure of human succinic semialdehyde dehydrogenase gene: identification of promoter region and alternatively processed isoforms. Mol Genet Metab. 2002 Aug;76(4):348-62. doi: 10.1016/s1096-7192(02)00105-1. Citation on PubMed
- Gordon N. Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria). Eur J Paediatr Neurol. 2004;8(5):261-5. doi: 10.1016/j.ejpn.2004.06.004. Citation on PubMed
- Pearl PL, Gibson KM, Acosta MT, Vezina LG, Theodore WH, Rogawski MA, Novotny EJ, Gropman A, Conry JA, Berry GT, Tuchman M. Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. Neurology. 2003 May 13;60(9):1413-7. doi: 10.1212/01.wnl.0000059549.70717.80. Citation on PubMed
- Pearl PL, Novotny EJ, Acosta MT, Jakobs C, Gibson KM. Succinic semialdehyde dehydrogenase deficiency in children and adults. Ann Neurol. 2003;54 Suppl 6:S73-80. doi: 10.1002/ana.10629. Citation on PubMed
- Tokatly Latzer I, Roullet JB, Cesaro S, DiBacco ML, Arning E, Rotenberg A, Lee HHC, Opladen T, Jeltsch K, Garcia-Cazorla A, Julia-Palacios N, Gibson KM, Bertoldi M, Pearl PL. Phenotypic correlates of structural and functional protein impairments resultant from ALDH5A1 variants. Hum Genet. 2023 Dec;142(12):1755-1776. doi: 10.1007/s00439-023-02613-6. Epub 2023 Nov 14. Citation on PubMed
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