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Succinate-semialdehyde dehydrogenase deficiency(SSADHD)

MedGen UID:
124340
Concept ID:
C0268631
Disease or Syndrome
Synonyms: 4-hydroxybutyric aciduria; Gamma-hydroxybutyric acidemia; Gamma-hydroxybutyricaciduria; SSADHD; Succinic Semialdehyde Dehydrogenase Deficiency; Succinic semialdehyde dehydrogenase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Succinic semialdehyde dehydrogenase deficiency (49748000); 4--Hydroxybutyric aciduria (49748000); Gamma-hydroxybutyric acidemia (49748000); Succinate-semialdehyde dehydrogenase deficiency (49748000); GABAuria (49748000); gamma-Hydroxybutyric aciduria (49748000); GABA metabolic defect (49748000)
 
Gene: ALDH5A1
Cytogenetic location: 6p22.3
OMIM: 271980

Disease characteristics

Excerpted from the GeneReview: Succinic Semialdehyde Dehydrogenase Deficiency
Succinic semialdehyde dehydrogenase (SSADH) deficiency is characterized by psychomotor retardation, childhood-onset hypotonia, and ataxia. Seizures occur in more than 50% of affected individuals. Hyperkinetic behavior, aggression, self-injurious behaviors, hallucinations, and sleep disturbances have been reported in nearly half of all patients, and are common in older individuals. Basal ganglia signs such as choreoathetosis, dystonia, and myoclonus have been reported in a few individuals with earlier-onset, more severe disease. Involvement beyond the central nervous system has not been described. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Phillip L Pearl  |  Adrianne M Dorsey  |  Emily S Barrios, et. al.   view full author information

Additional descriptions

From OMIM
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive neurologic disorder in which an enzyme defect in the GABA degradation pathway causes a consecutive elevation of gamma-hydroxybutyric acid (GHB) and GABA. The clinical features include developmental delay, hypotonia, mental retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances (summary by Reis et al., 2012).  http://www.omim.org/entry/271980
From GHR
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.  http://ghr.nlm.nih.gov/condition/succinic-semialdehyde-dehydrogenase-deficiency

Clinical features

Abnormality of eye movement
MedGen UID:
424997
Concept ID:
CN000464
Finding
An abnormality in voluntary or involuntary eye movements or their control.
Psychosis
MedGen UID:
504566
Concept ID:
CN000666
Finding
A condition characterized by changes of personality and thought patterns often accompanied by hallucinations and delusional beliefs.
Autism
MedGen UID:
504569
Concept ID:
CN000674
Finding
Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV).
Aggressive behavior
MedGen UID:
504570
Concept ID:
CN000675
Finding
Aggressive behavior can denote verbal aggression, physical aggression against objects, physical aggression against people, and may also include aggression towards oneself.
Delayed speech and language development
MedGen UID:
504583
Concept ID:
CN000706
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Ataxia
MedGen UID:
504767
Concept ID:
CN001146
Finding
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
504779
Concept ID:
CN001164
Finding
A type of `Developmental delay` (HP:0001263) characterized by a delay in acquiring motor skills.
Generalized tonic-clonic seizures
MedGen UID:
505078
Concept ID:
CN001871
Finding
Generalized tonic-clonic seizures are `generalized seizures` (HP:0002197) with bilateral symmetrical tonic contraction then bilateral clonic contractions of somatic muscles usually associated with autonomic phenomena.
Absence seizures
MedGen UID:
505114
Concept ID:
CN001921
Finding
Recurrent absence seizures are `generalized seizures` (HP:0002197) and are characterized by a loss of consciousness, thus, are a form of `dialeptic seizures` (HP:0011146).
Generalized myoclonic seizures
MedGen UID:
505115
Concept ID:
CN001923
Finding
Seizures with sudden, brief (< 100 msec) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal).
Status epilepticus
MedGen UID:
505118
Concept ID:
CN001933
Finding
Seizures lasting for more than 30 minutes or longer or multiple seizures repeated frequently without regaining consciousness between seizures.
Hyperkinesis
MedGen UID:
505250
Concept ID:
CN002258
Finding
Motor hyperactivity with excessive movement of muscles of the body as a whole.
Self-injurious behavior
MedGen UID:
506521
Concept ID:
CN117607
Finding
Aggression towards oneself.
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGSuccinate-semialdehyde dehydrogenase deficiency

Recent clinical studies

Etiology

Aligianis IA, Farndon PA, Gray RG, Heath SK, Kilby M, Gibson KM, Akaboshi S
J Inherit Metab Dis 2002 Oct;25(6):517-8. PMID: 12555945

Diagnosis

Aligianis IA, Farndon PA, Gray RG, Heath SK, Kilby M, Gibson KM, Akaboshi S
J Inherit Metab Dis 2002 Oct;25(6):517-8. PMID: 12555945

Prognosis

Aligianis IA, Farndon PA, Gray RG, Heath SK, Kilby M, Gibson KM, Akaboshi S
J Inherit Metab Dis 2002 Oct;25(6):517-8. PMID: 12555945

Clinical prediction guides

Gupta M, Jansen EE, Senephansiri H, Jakobs C, Snead OC, Grompe M, Gibson KM
Mol Ther 2004 Apr;9(4):527-39. doi: 10.1016/j.ymthe.2004.01.013. PMID: 15093183
Aligianis IA, Farndon PA, Gray RG, Heath SK, Kilby M, Gibson KM, Akaboshi S
J Inherit Metab Dis 2002 Oct;25(6):517-8. PMID: 12555945

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