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)

Ten autopsy cases of Progressive Supranuclear Palsy (PSP) are reported. Age at onset ranged from 16 to 67 years and the duration of illness 3 to 24 years. The clinical features were aggressive mental retardation in 4 cases with early onset, paroxysmal dysequilibrium, ophthalmoplegia, rigidity and akinesia, pseudobulbar palsy and variable degrees of dementia. Neuropathology showed widespread neurofibrillary degeneration associated with system-bound neuronal loss and gliosis in subcortical areas, particularly affecting the subthalamic nucleus, substantia nigra, brainstem tegmentum and dentate nuclei, with no or little involvement of the cerebral cortex. The distribution of the lesions and the ultrastructure of the neurofibrillary tangles made of 15 nm straight filaments (seen in one case) in PSP are different from postencephalitic parkinsonism, Guam Parkinson-dementia complex and brainstem affection in (pre)senile dementia. Post-mortem biochemical analysis of two brains disclosed severe reduction of tyrosine hydroxylase, the key synthetic enzyme of the catecholamine pathway, not only in the nigrostriatal system as seen in Parkinson's disease, but in most areas of the brain-stem and limbic system. The implication and possible pathogenic and therapeutic significance of these biochemical findings are discussed. The etiology of PSP and its nosological position within the degenerative extrapyramidal disorders remain unknown.
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PMID:Progressive supranuclear palsy: clinico-pathological and biochemical studies. 610 28

We report a patient with frontotemporal degeneration and parkinsonism with mental retardation. The patient was a 54-year-old man who had parkinsonism that resembled progressive supranuclear palsy, frontotemporal degeneration and myoclonus. His family included many affected members. Neuropathologically, there was degeneration of the frontal and temporal cortices, the basal ganglia, the brainstem and the cerebellum. Microscopically, neuronal loss was severe in the frontal and temporal cortex, the globus pallidus, substantia nigra, red nucleus and dentate nucleus. Fibrillary changes were found in neurons and glia that were immunostained for tau. Although we could not define the genetic abnormalities, we thought that this case might have involved frontotemporal dementia and parkinsonism linked to chromosome 17.
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PMID:A case of frontotemporal dementia and parkinsonism of early onset with progressive supranuclear palsy-like features. 1122 Jun 96

Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive (AR) disorder characterized by motor symptoms as such as dystonia or parkinsonism, mental retardation, retinitis pigmentosa and iron accumulation in the brain. As many neurodegenerative conditions have similar clinical features we screened a number of adult and childhood onset movement disorders for PANK2 mutation. This included cases with neurodegeneration and brain iron accumulation, corticobasal degeneartion, progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atropy, giant axonal neuropathy (GAN), neuroaxonal dystrophy (NAD), Guam dementia and HARP syndrome (pallido-pyramidal syndrome and hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration). From our series of patients one patient with PKAN and a progressive severe dystonic syndrome, cerebellar ataxia, retinitis pigmentosa and eventual anarthria had a novel combination of two compound heterozygote mutations identified in the PANK2 gene, G-->A transition at base 1238 (G411R) and a C-->A transition at base 1184 (A395E). In the patient with HARP syndrome two compound heterozygote mutations (Met327Thr and IVS5-1 G to T) in the PANK2 gene were found. No other mutations were found in any of the other patient groups, suggesting that PANK2 mutations are not associated with the aetiology of these adult degenerative conditions and confirms the genetic heterogeneity in neurodegeneration with brain iron accumulation.
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PMID:PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease. 1696 35