Description
Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.
Frequency
Approximately 350 people with succinic semialdehyde dehydrogenase deficiency have been reported worldwide.
Causes
Mutations in the ALDH5A1 gene cause succinic semialdehyde dehydrogenase deficiency. The ALDH5A1 gene provides instructions for producing the succinic semialdehyde dehydrogenase enzyme. This enzyme 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.
A shortage (deficiency) of succinic semialdehyde dehydrogenase leads to an increase in the amount of GABA and a related molecule called gamma-hydroxybutyrate (GHB) in the body, particularly the brain and spinal cord (central nervous system). It is unclear how an increase in GABA and GHB causes developmental delay, seizures, and other signs and symptoms of succinic semialdehyde dehydrogenase deficiency.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- 4-hydroxybutyric aciduria
- 4-hydroxybutyricaciduria
- Gamma-hydroxybutyric acidemia
- Gamma-hydroxybutyric aciduria
- SSADH deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
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
- Gibson KM, Gupta M, Pearl PL, Tuchman M, Vezina LG, Snead OC 3rd, Smit LM, Jakobs C. Significant behavioral disturbances in succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria). Biol Psychiatry. 2003 Oct 1;54(7):763-8. doi: 10.1016/s0006-3223(03)00113-6. Citation on PubMed
- Gibson KM. Gamma-hydroxybutyric aciduria: a biochemist's education from a heritable disorder of GABA metabolism. J Inherit Metab Dis. 2005;28(3):247-65. doi: 10.1007/s10545-005-7053-4. 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
- Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitter disorders. J Child Neurol. 2007 May;22(5):606-16. doi: 10.1177/0883073807302619. Citation on PubMed
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