4-Hydroxybutyric aciduria

Rahbeeni, Zuhair; Özand, Pinar; Rashed, Mohamed S.; Gascon, Generoso G.; Nasser, Maliha; Odaib, A. Al; Amoudi, M.; Nester, Michael; Garawi, S. Al; Brismar, J.

doi:10.1016/0387-7604(94)90098-1

Cited by 40 publications

(14 citation statements)

References 23 publications

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“…We also report a range of EEG findings based on a literature review capturing 25 published cases with EEG data available [11][12][13][14][15][16]18,19 and combined with 9 patients from our cohort (see table 2). Abnormalities include generalized and focal epileptiform discharges, photosensitivity, background slowing, and sleep spindle asynchrony.…”

Section: Resultsmentioning

confidence: 99%

“…Abnormalities include generalized and focal epileptiform discharges, photosensitivity, background slowing, and sleep spindle asynchrony. [11][12][13][14][15][16][17][18][19]21 These revealed T2 hyperintensities in multiple regions, most commonly of the globus pallidus (see table 2). The explanation for epilepsy in nearly half of SSADH-deficient patients is unclear.…”

Section: Resultsmentioning

confidence: 99%

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Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

Pearl¹,

Gibson²,

Acosta³

et al. 2003

Neurology

191

158

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Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting CNS gamma-aminobutyric acid (GABA) degradation. SSADH, in conjunction with GABA transaminase, converts GABA to succinate. In the absence of SSADH, GABA is converted to 4-OH-butyrate. The presence of 4-OH-butyrate, a highly volatile compound, may be undetected on routine organic acid analysis. Urine organic acid testing was modified at the authors' institution in 1999 to screen for the excretion of 4-OH-butyrate by selective ion monitoring gas chromatography-mass spectrometry in addition to total ion chromatography. Since then, five patients with 4-hydroxybutyric aciduria have been identified. The authors add the clinical, neuroimaging, and EEG findings from a new cohort of patients to 51 patients reported in the literature with clinical details. Ages ranged from 1 to 21 years at diagnosis. Clinical findings include mild-moderate mental retardation, disproportionate language dysfunction, hypotonia, hyporeflexia, autistic behaviors, seizures, and hallucinations. Brain MRI performed in five patients at the authors' institution revealed symmetric increased T2 signal in the globus pallidi. SSADH deficiency is an under-recognized, potentially manageable neurometabolic disorder. Urine organic acid analysis should include a sensitive method for the detection of 4-hydroxybutyrate and should be obtained from patients with mental retardation or neuropsychiatric disturbance of unknown etiology.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

Pearl¹,

Gibson²,

Acosta³

et al. 2003

Neurology

191

158

View full text Add to dashboard Cite

show abstract

“…Hyporeflexia, behaviour problems, strabismus, gastrointestinal symptoms and poor feeding in the neonatal period may be present . Episodes of unexplained lethargy and developmental regression or a more fulminant course in early-onset patients have also been reported in some SSADHdeficient individuals (Gibson and Jakobs 2001;Gibson et al 1998;Jakobs et al 1993;Pearl et al 2003;Rahbeeni et al 1994). The most common abnormalities found in magnetic resonance neuroimaging scanning involve the globus pallidus bilaterally and symmetrically and the subcortical white matter.…”

Section: Introductionmentioning

confidence: 89%

Evidence for oxidative stress in tissues derived from succinate semialdehyde dehydrogenase‐deficient mice

Latini

Scussiato

Leipnitz

et al. 2007

J of Inher Metab Disea

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Animal models of inborn errors of metabolism are useful for investigating the pathogenesis associated with the corresponding human disease. Since the mechanisms involved in the pathophysiology of succinate semialdehyde dehydrogenase (SSADH) deficiency (Aldh5a1; OMIM 271980) are still not established, in the present study we evaluated the tissue antioxidant defences and lipid peroxidation in various cerebral structures (cortex, cerebellum, thalamus and hippocampus) and in the liver of SSADH-deficient mice. The parameters analysed were total radical-trapping antioxidant potential (TRAP) and glutathione (GSH) levels, the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as thiobarbituric acid-reactive substances (TBARS). We first observed that the tissue nonenzymatic antioxidant defences were significantly reduced in the SSADH-deficient animals, particularly in the liver (decreased TRAP and GSH) and in the cerebral cortex (decreased GSH), as compared to the wild-type mice. Furthermore, SOD activity was significantly increased in the liver and cerebellum, whereas the activity of CAT was significantly higher in the thalamus. In contrast, GPx activity was significantly diminished in the hippocampus. Finally, we observed that lipid peroxidation (TBARS levels) was markedly increased in the liver and cerebral cortex, reflecting a high lipid oxidative damage in these tissues. Our data showing an imbalance between tissue antioxidant defences and oxidative attack strongly indicate that oxidative stress is involved in the pathophysiology of SSADH deficiency in mice, and likely the corresponding human disorder.

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“…Two additional reports indicated clinical improvement in ~ 1/3 of patients treated with VGB, without clinical details (Rahbeeni et al 1994; Gibson et al 1997). …”

Section: Figmentioning

confidence: 99%

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Vogel

Pearl

Theodore

et al. 2012

J of Inher Metab Disea

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Summary This review summarizes a presentation made at the retirement Symposium of Prof. 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. Active and potential clinical interventions, including vigabatrin, L-cycloserine, the GHB receptor antagonist NCS-382, and the ketogenic diet, are discussed. Several biomarkers to gauge clinical efficacy have been identified, including cerebrospinal fluid metabolites, neuropsychiatric testing, MRI, EEG, and measures of GABAergic function including (11C)flumazenil positron emission tomography (PET) and transcranial magnetic stimulation (TMS). Thirty years after its discovery, encompassing extensive studies in both patients and the corresponding murine model, we are now running an open-label trial of taurine intervention, and are poised to undertake a phase II trial of the GABAB receptor antagonist SGS742.

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4-Hydroxybutyric aciduria

Cited by 40 publications

References 23 publications

Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

Evidence for oxidative stress in tissues derived from succinate semialdehyde dehydrogenase‐deficient mice

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

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