succinic semialdehyde dehydrogenase deficiency

A rare hereditary autosomal recessive neurologic disorder in which an enzyme defect in the GABA degradation pathway causes a consecutive elevation of gamma-hydroxybutyric acid (GHB) and GAMMA-AMINOBUTYRIC ACID (GABA). It is characterized by DEVELOPMENTAL DISABILITIES; INTELLECTUAL DISABILITIES; HYPOTONIA; ATAXIA; SEIZURES; AGGRESSION, hyperkinetic behavior, and sleep disturbances. Mutations in the ALDH5A1 gene have been identified. OMIM: 271980

Also Known As:

Networked: 196 relevant articles (9 outcomes, 11 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Status Epilepticus (Complex Partial Status Epilepticus)
2.	Narcolepsy
3.	Seizures (Absence Seizure)
4.	Fragile X Syndrome (Martin Bell Syndrome)
5.	succinic semialdehyde dehydrogenase deficiency

Experts

1.	Gibson, K Michael: 54 articles (01/2022 - 07/2002)
2.	Pearl, Phillip L: 34 articles (02/2022 - 01/2003)
3.	Gibson, K M: 28 articles (02/2018 - 03/2001)
4.	Jakobs, Cornelis: 18 articles (09/2015 - 07/2002)
5.	Jakobs, C: 17 articles (01/2012 - 03/2001)
6.	Snead, O Carter: 14 articles (03/2009 - 07/2002)
7.	Roullet, Jean-Baptiste: 13 articles (01/2022 - 01/2018)
8.	Salomons, Gajja S: 10 articles (11/2020 - 12/2003)
9.	Salomons, G S: 10 articles (06/2017 - 03/2001)
10.	Pearl, P L: 9 articles (01/2017 - 05/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to succinic semialdehyde dehydrogenase deficiency:

1.	gamma-Aminobutyric Acid (GABA)IBA 01/01/2006 - "Elucidation of the precise fundamental mechanisms of the perturbation of the GABA(A)R-mediated function in SSADH(-/-) mice could lead to the development of novel treatment modalities designed to reduce the neurological morbidity in children with SSADH deficiency." 05/01/2013 - "Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism." 07/16/2023 - "Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare neurometabolic disorder caused by disruption of the gamma-aminobutyric acid (GABA) pathway. " 01/01/2023 - "Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare inherited metabolic disorder caused by a defect of γ-aminobutyrate (GABA) catabolism. " 12/16/2022 - "Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is an autosomal recessive gamma-aminobutyric acid (GABA) metabolism disorder that can arise due to ALDH5A1 mutations, resulting in severe, progressive, untreatable neurodegeneration. "
2.	Succinate-Semialdehyde Dehydrogenase (Succinic Semialdehyde Dehydrogenase)IBA 11/01/2021 - "This study reviews the fundamental roles of pre-supplementary motor area (SMA) and SMA-proper responsible for speech-motor functions and auditory perception in succinic semialdehyde dehydrogenase (SSADH) deficiency. " 05/01/2013 - "Dr. Cornelis Jakobs in November of 2011, highlighting the progress toward clinical trials in succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder first recognized in 1981. " 11/01/2021 - "Pathogenic variants in ALDH5A1 cause succinic semialdehyde dehydrogenase (SSADH) deficiency, with >180 cases reported worldwide. " 01/01/2021 - "Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder. " 11/10/2020 - "To determine genotype-phenotype correlation in succinic semialdehyde dehydrogenase (SSADH) deficiency. "
3.	4-hydroxybutyric acidIBA 09/01/2019 - "This preliminary study suggests that succinic semialdehyde dehydrogenase deficiency may be identified in newborn and post-newborn dried bloodspots via quantitation of gamma-hydroxybutyric acid, while forming the platform for more extensive studies in affected and unaffected dried bloodspots." 09/01/2019 - "Here, we examined the hypothesis that succinic semialdehyde dehydrogenase deficiency could be identified via measurement of gamma-hydroxybutyric acid in newborn and post-newborn dried bloodspots. " 07/01/2013 - "Dried blood spot (DBS) cards from patients affected with SSADH deficiency were compared with 2831 archival DBS cards for gamma-hydroxybutyric acid content. " 02/01/2012 - "The diagnosis of SSADH deficiency was confirmed by an increase in 4-hydroxybutyric acid and heteroallelic mutation in the ALDH5A1 gene. " 01/01/2004 - "Sedation with 4-hydroxybutyric acid: a potential pitfall in the diagnosis of SSADH deficiency."
4.	VigabatrinFDA Link 11/01/2003 - "Our results suggest that GHB quantification in physiological fluids may be a useful laboratory parameter for monitoring efficacy of vigabatrin treatment in SSADH deficiency." 01/01/2012 - "Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency." 01/01/2003 - "Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency." 01/01/1996 - "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." 01/01/1995 - "Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency."
5.	TaurineFDA Link 03/18/2014 - "This study provides Class IV evidence that for patients with succinic semialdehyde dehydrogenase deficiency, taurine does not significantly improve adaptive behavior. " 03/18/2014 - "The objective of this open-label study was primarily to assess the effect of taurine on adaptive behavior and secondarily to collect safety and tolerability data in patients with succinic semialdehyde dehydrogenase deficiency. " 01/01/2016 - "Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency." 03/18/2014 - "Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA." 08/01/2016 - "Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency."
6.	Biomarkers (Surrogate Marker)IBA 01/01/2020 - "Novel biomarkers and age-related metabolite correlations in plasma and dried blood spots from patients with succinic semialdehyde dehydrogenase deficiency." 01/01/2019 - "Age-related phenotype and biomarker changes in SSADH deficiency." 12/01/2023 - "Succinic semialdehyde dehydrogenase deficiency: A model of neurocircuit imbalances in autism and potential insight into new biomarkers." 01/01/2016 - "Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency." 11/01/2016 - "Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism."
7.	(3-aminopropyl)(n-butyl)phosphinic acidIBA 11/01/2021 - "Our data do not support the current use of SGS-742 in succinic semialdehyde dehydrogenase deficiency.Trial" 11/01/2021 - "This was a single-center randomized, double-blind crossover phase II clinical trial of SGS-742 versus placebo in patients with succinic semialdehyde dehydrogenase deficiency. " 11/01/2021 - "Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency. " 01/01/2018 - "Three drugs are presently in clinical trials: acamprosate and ganoxolon for Fragile X syndrome and SGS-742 for SSADH deficiency. " 11/01/2021 - "We examined safety, tolerability, and efficacy of SGS-742, a γ-aminobutyric acid B (GABA-B) receptor antagonist, in patients with succinic semialdehyde dehydrogenase deficiency. "
8.	Aminobutyrates (Aminobutyric Acid)IBA 01/01/2023 - "Our findings indicate that increased γ-aminobutyric acid concentration is associated with reduced sensory-evoked beta and gamma activity and impaired neuronal synchronization in patients with succinic semialdehyde dehydrogenase deficiency. " 01/01/2023 - "Reduced evoked cortical beta and gamma activity and neuronal synchronization in succinic semialdehyde dehydrogenase deficiency, a disorder of γ-aminobutyric acid metabolism." 03/01/2015 - "Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive metabolic disorder affecting γ-aminobutyric acid degradation. " 11/01/2021 - "Enzyme Replacement Therapy for Succinic Semialdehyde Dehydrogenase Deficiency: Relevance in γ-Aminobutyric Acid Plasticity." 01/01/2023 - "Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessively inherited metabolic disorder of γ-aminobutyric acid catabolism manifested by intellectual disability, expressive aphasia, movement disorders, psychiatric ailments and epilepsy. "
9.	Neurotransmitter Agents (Neurotransmitter)IBA 06/01/2011 - "Inherited deficiency of SSADH results in accumulation of the neuromodulator γ-hydroxybutyrate (GHB), which likely contributes to some aspects of the neurological phenotype of SSADH deficiency (MIM #271980). " 09/01/2006 - "SSADH deficiency is the most commonly occurring of the inherited disorders of neurotransmitters. " 01/01/2003 - "Succinic semialdehyde dehydrogenase deficiency may be an underrecognized neurometabolic disorder with a nonspecific and wide phenotypic spectrum, and carries implications for a comprehensive fundamental understanding of interrelations between multiple neurotransmitter systems." 07/03/2012 - "This first demonstration of altered GABA(B)-ergic function in patients with SSADH deficiency may help to explain clinical features of the disease, and suggest pathophysiologic mechanisms in other neurotransmitter-related disorders." 01/01/2018 - "The highest GABA levels are found in the primary GABA neurotransmitter disorder SSADH deficiency. "
10.	Sodium Oxybate (gamma Hydroxybutyrate)FDA Link 09/01/2019 - "Gamma-Hydroxybutyrate content in dried bloodspots facilitates newborn detection of succinic semialdehyde dehydrogenase deficiency." 01/01/2017 - "Gamma-Hydroxybutyrate (GHB) Content in Hair Samples Correlates Negatively with Age in Succinic Semialdehyde Dehydrogenase Deficiency." 01/01/2002 - "A unique mouse model for succinic semialdehyde dehydrogenase deficiency with implications for gamma hydroxybutyrate intoxication." 12/01/2007 - "SSADH deficiency in humans is associated with excessive elevation of GABA and gamma-hydroxybutyrate (GHB). " 01/01/2017 - "Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). "

Therapies and Procedures

1.	Transcranial Magnetic Stimulation 11/01/2021 - "Transcranial Magnetic Stimulation in Succinic Semialdehyde Dehydrogenase Deficiency: A Measure of Maturational Trajectory of Cortical Excitability." 07/03/2012 - "We quantified the magnitude of excitation and inhibition in primary motor cortex (M1) in patients with SSADH deficiency, their parents (obligate heterozygotes), age-matched healthy young controls, and healthy adults using single and paired pulse transcranial magnetic stimulation (TMS). " 01/01/2016 - "We tested the hypothesis that patients with succinic semialdehyde dehydrogenase (SSADH) deficiency on taurine would have decreased cortical excitability as measured by transcranial magnetic stimulation (TMS) and improved cognition, due to taurine's partial GABA(A and B) receptor agonist effects and rescue in the null mouse model from status epilepticus and premature lethality. "
2.	Therapeutics 01/01/2020 - "Serotonergic and concomitant dopaminergic therapy may be a viable treatment regimen for SSADH deficiency patients presenting with OCD symptoms." 11/01/2021 - "Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency. " 01/01/1995 - "Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency." 01/01/1993 - "4-Hydroxybutyric aciduria: clinical findings and vigabatrin therapy." 06/01/1992 - "Further evaluation of Vigabatrin therapy in 4-hydroxybutyric aciduria."
3.	Catheters 02/01/2011 - "4-Hydroxybutyric aciduria associated with catheter usage: a diagnostic pitfall in the identification of SSADH deficiency."
4.	Enzyme Replacement Therapy 11/01/2021 - "Enzyme Replacement Therapy for Succinic Semialdehyde Dehydrogenase Deficiency: Relevance in γ-Aminobutyric Acid Plasticity."
5.	Ketogenic Diet 04/01/2008 - "We tested the hypothesis that a ketogenic diet (KD) would improve outcome in an animal model of SSADH deficiency, the SSADH knockout mouse (Aldh5a1-/-). "