Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency.

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.
Authors	Maria T Acosta, Jeeva Munasinghe, Phillip L Pearl, Maneesh Gupta, Andrey Finegersh, K Michael Gibson, William H Theodore
Journal	Journal of child neurology (J Child Neurol) Vol. 25 Issue 12 Pg. 1457-61 (Dec 2010) ISSN: 1708-8283 [Electronic] United States
PMID	20445195 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Succinate-Semialdehyde Dehydrogenase
Topics	Adolescent Adult Amino Acid Metabolism, Inborn Errors (enzymology, genetics, pathology) Animals Atrophy Brain Diseases, Metabolic, Inborn (diagnostic imaging, enzymology, pathology) Cerebellar Diseases (diagnostic imaging, enzymology, pathology) Child Developmental Disabilities Disease Models, Animal Female Humans Magnetic Resonance Imaging Male Mice Mice, Knockout Mice, Transgenic Middle Aged Radiography Random Allocation Succinate-Semialdehyde Dehydrogenase (deficiency, genetics) Young Adult

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