Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Canavan's disease is characterized by megalencephaly, leukodystrophy and early motor and mental retardation. On computerized tomography and magnetic resonance imaging, severe changes compatible with white matter disease due to demyelination is observed. It has been demonstrated that urinary N-acetylaspartate levels are increased because of a deficiency of aspartoacylase (N-acyl-L-aspartate aminohydrolase) in these patients. In this study, with the use of proton nuclear magnetic resonance spectroscopy, we were able to demonstrate elevated levels of N-acetylaspartate compared to choline and creatine in the frontal region white matter of three patients. The in vivo measurement of N-acetylaspartate, choline and creatine in the brain by magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease.
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PMID:Use of localized proton nuclear magnetic resonance spectroscopy in Canavan's disease. 1002 64

Canavan disease (CD) is an autosomal recessive leukodystrophy characterized by spongy degeneration of the brain. The clinical features of CD are hypotonia, megalencephaly, and mental retardation leading to early death. While aspartoacylase (ASPA) activity increases with age in the wild type mouse brain, there is no ASPA activity in the CD mouse brain. So far ASPA deficiency and elevated NAA have been ascribed with the CD. Other factors affecting the brain that result from ASPA deficiency may lead pathophysiology of CD. The NMR spectra and amino acid analysis showed lower levels of glutamate and gamma-aminobutyric acid in the CD mouse brain compared to the wild type. Microarray gene expression on CD mouse brain showed glutamate transporter-EAAT4 and gamma-aminobutyric acid-A receptor, subunit alpha6 (GABRA6) were lower 9.7- and 119.1-fold, respectively. Serine proteinase inhibitor 2 (Spi2) was 29.9-fold higher in the CD mouse brain compared to the wild type. The decrease of GABRA6 and high expression of Spi2 in CD mouse brain were also confirmed by real-time RT-PCR. This first report showing abnormal expression of EAAT4, GABRA6, Spi2 combined with lower levels of glutamate and GABA are likely to be associated with the pathophysiology of CD.
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PMID:Expression of glutamate transporter, GABRA6, serine proteinase inhibitor 2 and low levels of glutamate and GABA in the brain of knock-out mouse for Canavan disease. 1290 86

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and gamma-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.
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PMID:Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. 1501 27

Canavan disease (CD) is an autosomal recessive disorder, characterized by spongy degeneration of the brain. Patients with CD have aspartoacylase (ASPA) deficiency, which results accumulation of N-acetylaspartic acid (NAA) in the brain and elevated excretion of urinary NAA. Clinically, patients with CD have macrocephaly, mental retardation and hypotonia. A knockout mouse for CD which was engineered, also has ASPA deficiency and elevated NAA. Molecular studies of the mouse brain showed abnormal expression of multiple genes in addition to ASPA deficiency. Adenoassociated virus mediated gene transfer and stem cell therapy in the knockout mouse are the latest attempts to alter pathophysiology in the CD mouse.
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PMID:Canavan disease: studies on the knockout mouse. 1680 6

Canavan disease is a severe autosomal recessive leukodystrophy characterized by macrocephaly, ataxia, severe motor and mental retardation, dysmyelination, and progressive spongial atrophy of the brain. The human aspartoacylase (ASPA) gene, which catalyzes the deacetylation of N-acetyl-L-aspartate, is mutated in Canavan disease. In the presented family sequencing analysis for the aspartoacylase gene was performed on the blood samples of the parents as the affected child had died due to Canavan disease. After the mutation was detected, prenatal diagnosis was also performed and heterozygous Y88X mutation was detected in the fetus. In this report, we present a novel mutation Y88X within the aspartoacylase gene in a consanguineous family with an affected child diagnosed as Canavan disease.
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PMID:A novel aspartoacylase (ASPA) gene mutation in Canavan disease. 2246 86

Canavan disease (CD) is an autosomal recessive inherited disorder characterized by spongy degeneration of the brain. The deficiency of aspartoacylase (ASPA), resulting in the accumulation of N-acetyl aspartic acid (NAA) in the brain, plays an important role in the pathogenesis of the disease. The cardinal features of this neurodegenerative disease are macrocephaly, mental retardation, and hypotonia. Magnetic resonance imaging (MRI) of the brain generally shows diffuse white matter degeneration and also elevated excretion of urinary NAA is usually seen. A large number of mutations were identified to date. We report here a 9 months old girl with Canavan Disease and a homozygous c.79G>A mutation in the ASPA gene, detected for the first time in Turkish population.
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PMID:A mutation of aspartoacylase gene in a Turkish patient with Canavan disease. 2261 36