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Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency.

ABSTRACT: The pathophysiology of succinic semialdehyde dehydrogenase (SSADH) deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH), and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients.

SUBMITTER: Niemi AK

PROVIDER: S-EPMC5121295 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency.

Niemi Anna-Kaisa AK Brown Candida C Moore Tereza T Enns Gregory M GM Cowan Tina M TM

Molecular genetics and metabolism reports 20140401

The pathophysiology of succinic semialdehyde dehydrogenase (SSADH) deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH), and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, ta ...[more]

PMID: 27896081

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Succinic Semialdehyde Dehydrogenase Deficiency: An Update.

Project description:Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter ?-amino butyric acid (GABA). The disease is caused by impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degrees of mental retardation, autism, ataxia, and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved curative therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials, and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs, and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between researchers and patients.

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Polysomnographic abnormalities in succinic semialdehyde dehydrogenase (SSADH) deficiency.

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| S-EPMC5509553 | biostudies-literature

Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency.

Project description:Human succinic semialdehyde dehydrogenase deficiency, an autosomal recessive disorder of ?-aminobutyric acid (GABA) catabolism, was modeled by a murine model sharing the phenotype of ataxia and seizures. Magnetic resonance imaging (MRI) with volumetry was obtained on 7 patients versus controls, and MRI with stereology was derived in 3 murine genotypes: null, wild-type, and heterozygous mutants. All patients had T1 hypointensity and T2 hyperintensity in globus pallidus, and 5 also had similar changes in subthalamic and cerebellar dentate nuclei. There was a trend for patients to have a smaller cerebellar vermis. Homozygous null mice had significantly lower total brain and cerebellar volumes than wild-types and heterozygotes. Stereology confirmed cerebellar atrophy and was otherwise normal in multiple regions. Cerebellar volume loss is present in the murine disorder with a trend for cerebellar atrophy in patients. Reduced cerebellar volume can reflect neurodegeneration and may be related to the clinical manifestations.

| S-EPMC3155424 | biostudies-literature

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OCD symptoms in succinic semialdehyde dehydrogenase (SSADH) deficiency: a case report.

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Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA.

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