Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency.
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.
Acosta
Maria T
MT
Clinical Epilepsy Section, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Munasinghe
Jeeva
J
Pearl
Phillip L
PL
Gupta
Maneesh
M
Finegersh
Andrey
A
Gibson
K Michael
KM
Theodore
William H
WH
D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001284:Atrophy; D020739:Brain Diseases, Metabolic, Inborn / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology*; D002526:Cerebellar Diseases / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology*; D002648:Child; D002658:Developmental Disabilities; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D011859:Radiography; D011897:Random Allocation; D050644:Succinate-Semialdehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics; D055815:Young Adult
D050644:Succinate-Semialdehyde Dehydrogenase
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