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Succinic semialdehyde dehydrogenase deficiency


Other Names:
4-hydroxybutyric aciduria; Gamma-hydroxybutyricaciduria; SSADH deficiency; 4-hydroxybutyric aciduria; Gamma-hydroxybutyricaciduria; SSADH deficiency; GABA metabolic defect See More
Categories:
Succinic semialdehyde dehydrogenase (SSADH) deficiency is a disorder that can cause a variety of neurological and neuromuscular problems. The signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. Some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems.[1][2] SSADH deficiency is caused by mutations in the ALDH5A1 gene and is inherited in an autosomal recessive manner.[2] Management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues.[3]
Last updated: 9/25/2013
People with succinic semialdehyde dehydrogenase deficiency (SSADH) 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, 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 SSADH include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.[2]
Last updated: 9/25/2013

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Ataxia 0001251
Global developmental delay 0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Muscular hypotonia
Low or weak muscle tone
0001252
30%-79% of people have these symptoms
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Bilateral tonic-clonic seizure
Grand mal seizures
0002069
Generalized myoclonic seizure 0002123
Status epilepticus
Repeated seizures without recovery between them
0002133
Percent of people who have these symptoms is not available through HPO
Abnormality of eye movement
Abnormal eye movement
Abnormal eye movements
Eye movement abnormalities
Eye movement issue
[ more ] 		0000496
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Anxiety
Excessive, persistent worry and fear
0000739
Autism 0000717
Autosomal recessive inheritance 0000007
Decreased succinic semialdehyde dehydrogenase level 0032530
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
EEG abnormality 0002353
Elevated circulating gamma-aminobutyric acid concentration 0032529
Elevated CSF 4-hydroxybutyric acid concentration 0032532
Elevated CSF gamma-aminobutyric acid concentration 0032531
Elevated urinary 4-hydroxybutyric acid 0032528
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Generalized non-motor (absence) seizure
Brief seizures with staring spells
0002121
Hallucinations
Hallucination
Sensory hallucination
[ more ] 		0000738
Hyperactivity
More active than typical
0000752
Hyperkinetic movements
Muscle spasms
0002487
Hyporeflexia
Decreased reflex response
Decreased reflexes
[ more ] 		0001265
Increased level of gamma-aminobutyric acid in urine 0500253
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Motor delay 0001270
Psychomotor retardation 0025356
Psychosis 0000709
Self-injurious behavior
Self-injurious behaviour
0100716
Showing of 33 |
Last updated: 7/1/2020
Succinic semialdehyde dehydrogenase deficiency (SSADH) is caused by mutations in the ALDH5A1 gene. This gene provides instructions for producing the succinic semialdehyde dehydrogenase enzyme which 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.[2]
Last updated: 9/25/2013
Succinic semialdehyde dehydrogenase deficiency (SSADH) 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.[2]
Last updated: 9/25/2013
The diagnosis of succinic semialdehyde dehydrogenase (SSADH) deficiency is based upon a thorough clinical exam, the identification of features consistent with the condition, and a variety of specialized tests.[1] SSADH deficiency may first be suspected in late infancy or early childhood in individuals who have encephalopathy, a state in which brain function or structure is altered. The encephalopathy may be characterized by cognitive impairment; language deficit; poor muscle tone (hypotonia); seizures; decreased reflexes (hyporeflexia); and/or difficulty coordinating movements (ataxia). The diagnosis may be further suspected if urine organic acid analysis (a test that provides information about the substances the body discards through the urine) shows the presence of 4-hydroxybutyric acid. The diagnosis can be confirmed by an enzyme test showing deficiency of SSADH, or by genetic testing. ALDH5A1 is the only gene currently known to be associated with SSADH deficiency, and genetic testing can detect mutations in about 97% of affected individuals.[3]
Last updated: 9/25/2013
Treatment of succinic semialdehyde dehydrogenase deficiency (SSADH) is generally symptomatic and typically focuses on the treatment of seizures and neurobehavioral disturbances. Antiepileptic drugs (AEDs) that have proven to be effective in treating the seizures associated with this condition include carbamazepine and lamotrigine (LTG). Medications such as methylphenidate, thioridazine, risperidal, fluoxetine, and benzodiazepines appear to be effective at treating anxiety, aggressiveness, inattention, and hallucinations. Additional treatments may include physical and occupational therapy, sensory integration, and/or speech therapy.[3]
Last updated: 9/25/2013
There has been very limited extended follow-up of this condition from childhood into adulthood, so little is known about the long-term prognosis for individuals with the condition. Because the nature and severity of signs and symptoms are so variable among affected individuals, the prognosis and quality of life likely depend on the specific features each affected individual has.

In the limited information available about SSADH deficiency in older individuals, it has been reported that the main neurobehavioral features present in adolescents and adults with the condition include attention deficit, hyperactivity, anxiety, obsession-compulsion, aggressive behavior, hallucinatory episodes, and autistic features.[4] One article discussing how SSADH deficiency affected a single individual over 20 years reported that hyperactivity in adolescence evolved into moderate psychopathology in adulthood, which consisted of depression and obsession-compulsion. The authors of this study report that features in this individual are similar to those seen in others. They also stated that the individual did not have any further neurological deterioration over the 20-year period.[4] However, this information about a single affected individual may not apply to other individuals with the condition.
Last updated: 9/25/2013

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The main differential diagnoses include gamma-aminobutyric acid transaminase deficiency and homocarnosinosis (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Succinic semialdehyde dehydrogenase deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Succinic semialdehyde dehydrogenase deficiency. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Succinic semialdehyde dehydrogenase deficiency. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • How soon after birth can this be diagnosed? When is it known how severely an individual is affected? Is it possible to live a normal life? See answer


  1. Succinic Semialdehyde Dehydrogenase Deficiency. NORD. 2003; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1113/viewAbstract. Accessed 9/25/2013.
  2. Succinic semialdehyde dehydrogenase deficiency. Genetics Home Reference. June 2008; http://ghr.nlm.nih.gov/condition/succinic-semialdehyde-dehydrogenase-deficiency. Accessed 9/25/2013.
  3. Pearl PL, Dorsey AM, Barrios ES, Gibson KM. Succinic Semialdehyde Dehydrogenase Deficiency. GeneReviews. September 19, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1195/. Accessed 9/25/2013.
  4. Crutchfield SR, Haas RH, Nyhan WL, Gibson KM.. Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up. Developmental medicine and child neurology. November 2008; 50(11):880-881. http://www.ncbi.nlm.nih.gov/pubmed?term=18811705. Accessed 9/25/2013.