Cerebellar Atrophy in Human and Murine Succinic Semialdehyde Dehydrogenase Deficiency

Author:

Acosta Maria T.1,Munasinghe Jeeva2,Pearl Phillip L.3,Gupta Maneesh4,Finegersh Andrey5,Gibson K. Michael6,Theodore William H.5

Affiliation:

1. Clinical Epilepsy Section, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland, Department of Neurology, Children's National Medical Center, Washington, DC

2. Mouse Imaging Facility, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland

3. Clinical Epilepsy Section, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland, Department of Neurology, Children's National Medical Center, Washington, DC,

4. Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon

5. Clinical Epilepsy Section, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland

6. Department of Biological Sciences, Michigan Technological University, Houghton, Michigan

Abstract

Human succinic semialdehyde dehydrogenase deficiency, an autosomal recessive disorder of γ-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.

Publisher

SAGE Publications

Subject

Clinical Neurology,Pediatrics, Perinatology, and Child Health

Reference26 articles.

1. Molecular Cloning of the Mature NAD+-dependent Succinic Semialdehyde Dehydrogenase from Rat and Human

2. Stable isotope dilution analysis of 4-hydroxybutyric acid: An accurate method for quantification in physiological fluids and the prenatal diagnosis of 4-hydroxybutyric aciduria

3. Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

4. Neuropsychiatric Morbidity in Adolescent and Adult Succinic Semialdehyde Dehydrogenase Deficiency Patients

5. Pearl PL, Acosta MT, Wallis DD, et al. Dyskinetic features of succinate semialdehyde dehydrogenase deficiency, a GABA degradative defect. In: Fernandez-Alvarez E, Arzimanoglu A, Tolosa E, eds. Paediatric Movement Disorders: Progress in Understanding. Montrouge, France: John Libbey Eurotext; 2005:203-212.

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