Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Sialidosis is an autosomal recessive disease caused by the genetic deficiency of lysosomal sialidase, which catalyzes the catabolism of sialoglycoconjugates. The disease is associated with progressive impaired vision, macular cherry-red spots, and myoclonus (sialidosis type I) or with skeletal dysplasia, Hurler-like phenotype, dysostosis multiplex, mental retardation, and hepatosplenomegaly (sialidosis type II). We analyzed the effect of the missense mutations G68V, S182G, G227R, F260Y, L270F, A298V, G328S, and L363P, which are identified in the sialidosis type I and sialidosis type II patients, on the activity, stability, and intracellular distribution of sialidase. We found that three mutations, F260Y, L270F, and A298V, which are clustered in the same region on the surface of the sialidase molecule, dramatically reduced the enzyme activity and caused a rapid intralysosomal degradation of the expressed protein. We suggested that this region might be involved in sialidase binding with lysosomal cathepsin A and/or beta-galactosidase in the multienzyme lysosomal complex required for the expression of sialidase activity. Transgenic expression of mutants followed by density gradient centrifugation of cellular extracts confirmed this hypothesis and showed that sialidase deficiency in some sialidosis patients results from disruption of the lysosomal multienzyme complex.
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PMID:Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex. 1127 74

Finland and the Finns have been the subject of numerous genetic and genealogical studies, owing to enrichment of certain rare hereditary disorders in the Finnish population. Two types of NCL have so-far been found almost exclusively in Finland: Finnish variant late infantile NCL, vLINCL (CLN5), and the Northern epilepsy syndrome or Progressive epilepsy with mental retardation, EPMR (CLN8). The first symptoms of Finnish vLINCL are concentration problems or motor clumsiness by 3 to 6 years of age, followed by mental retardation, visual failure, ataxia, myoclonus, and epilepsy. Northern epilepsy, the newest member of the NCL family with the most protracted course, is characterized by the onset of generalized seizures between 5 and 10 years of age and subsequent progressive mental retardation. Visual problems are slight and late, while myoclonus has not been observed. Both the Finnish vLINCL and Northern epilepsy are pathologically characterized by intraneuronal cytoplasmic deposits of autofluorescent granules which are Luxol fast blue-, PAS-, and Sudan black B-positive in paraffin sections. In Northern epilepsy the intraneuronal storage process and neuronal destruction are generally of mild degree but highly selective and, in contrast to other forms of childhood onset NCL, the cerebellar cortex is relatively spared. By electron microscopy the storage bodies mainly contain rectilinear complex type and fingerprint profiles in Finnish vLINCL and structures resembling curvilinear profiles in Northern epilepsy. Mitochondrial ATP synthase subunit c is the main stored protein in both disorders. Both the DCLN5 and CLN8 genes encode putative membrane proteins with yet unknown functions. Furthermore, a well studied spontaneously occurring autosomal recessive mouse mutant, motor neuron degeneration (mnd) mouse, is a homolog for CLN8.
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PMID:Studies of homogenous populations: CLN5 and CLN8. 1133 69

Behavioral side effects associated with benzodiazepines (such as clonazepam, diazepam, and lorazepam) are an easily overlooked and underrecognized problem with individuals who have mental retardation and can be inadvertently confused with other behavioral or psychiatric conditions. Based upon a literature review, behavioral side effects occurred for 13.0% of 446 individuals with mental retardation who were prescribed benzodiazepines for either behavioral or psychiatric conditions (n = 138, 17.4%), epilepsy (n = 208, 15.4%), or other medical conditions such as myoclonus or cerebral palsy (n = 100, 2.0%). Behavioral side effects for individual benzodiazepines for which data were available ranged from 11.4% to 25.0%. Implications of nonrecognition are discussed, and clinical indicators suggesting review by appropriate medical personnel are provided.
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PMID:Benzodiazepine behavioral side effects: review and implications for individuals with mental retardation. 1218 78

Inherited metabolic disorders can cause onset of epilepsy in the first year of life. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as mental retardation, hypotonia and/or dystonia, or vigilance disturbances. The pathogenesis of seizures is multifaceted; inherited metabolic disorder can affect the balance between excitatory and inhibitory chemical mediators, eliminate an energetic substrate at the cerebral level, cause in utero brain malformation, or provoke acute brain lesions. Some clinical disorders that strongly suggest particular metabolic etiologies can be identified. For example, specific clinical signs and findings on electroencephalogram (EEG) are characteristic of pyridoxine-dependent seizures, and inherited metabolic disorders associated with early myoclonic encephalopathy are well defined. In most cases, however, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and EEG features that are difficult to classify into precise epileptic syndromes. Common characteristics of these seizures include onset in the first months of life; usually partial, multifocal; simple partial motor semiology; successive appearance of tonic seizures, spasms, and massive myoclonus; and resistance to antiepilepsy drugs. Inherited metabolic disorders must be considered in patients presenting with epilepsy and progressive neurologic worsening.
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PMID:Infantile epileptic syndromes and metabolic etiologies. 1259 51

Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, caused by a defect of another lysosomal protein, the protective protein. Three subtypes are recognized: the early infantile form, the late infantile form and the juvenile/adult form. We saw a patient with galactosialidosis of the juvenile/adult form, a 51-year-old Japanese man with angiokeratomas on both elbows and knees, myoclonus, ataxia, mental retardation and macular cherry-red spots. An electron-microscopic study of a skin biopsy showed membrane-limited vacuoles in the cytoplasm of the endothelial cells, pericytes and fibroblasts. Assays of enzymatic activity in cultured fibroblasts showed a marked decrease in both beta-galactosidase and neuraminidase (sialidase). The substance contained in the cytoplasmic vacuoles appears to be glycoproteins with sialic acid, which is a terminal glycosyl residue, because the cytoplasm of the endothelial cells of the vessels and pericytes are stained by the Limax flavus agglutinin, a lectin that binds specifically with sialic acid. This technology may be useful for easy investigation of the distribution of the accumulation of such substances in the central nervous system.
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PMID:A case of galactosialidosis. 1293 52

Lysosomal sialidase (EC 3.2.1.18) has a dual physiological function; it participates in intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in the sialidase gene NEU1, located on chromosome 6p21.3, result in autosomal recessive disorder, sialidosis, which is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. Sialidosis type I is a milder, late-onset, normosomatic form of the disorder. Type I patients develop visual defects, myoclonus syndrome, cherry-red macular spots, ataxia, hyperreflexia, and seizures. The severe early-onset form, sialidosis type II, is also associated with dysostosis multiplex, Hurler-like phenotype, mental retardation, and hepatosplenomegaly. We summarize information on the 34 unique mutations determined so far in the sialidase gene, including four novel missense and one novel nonsense mutations found in two Czech and two French sialidosis patients. The analysis of sialidase mutations in sialidosis revealed considerable molecular heterogeneity, reflecting the diversity of clinical phenotypes that make molecular diagnosis difficult. The majority of sialidosis patients have had missense mutations, many of which have been expressed; their effects on activity, stability, intracellular localization, and supramolecular organization of sialidase were studied. A structural model of sialidase allowed us to localize mutations in the sialidase molecule and to predict their impact on the tertiary structure and biochemical properties of the enzyme.
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PMID:Molecular pathology of NEU1 gene in sialidosis. 1451 45

We describe two couples of sibs from a southern Italian family affected by epilepsy, myoclonus, mental retardation and slight ataxia. Onset was between 4 and 12 years and the course slowly progressive. The clinical picture suggested the diagnosis of Unverricht-Lundborg disease. Molecular study excluded linkage to EPM1. Other possible causes of progressive myoclonus epilepsy were also excluded.
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PMID:Autosomal recessive progressive myoclonus epilepsy with ataxia and mental retardation. 1574 2

X-linked lissencephaly with abnormal genitalia is the first human disorder in which deficient tangential migration in the brain has been demonstrated. Male patients with X-linked lissencephaly with abnormal genitalia show intractable seizures, especially clonic convulsions or myoclonus from the first day of life, but neither infantile spasms nor hypsarrhythmia on electroencephalograms so far. Brain magnetic resonance imaging shows anterior pachygyria and posterior agyria with a mildly thick cortex, agenesis of the corpus callosum, and dysplastic basal ganglia. ARX, a paired-class homeobox gene with four polyalanine sequences, is a responsible gene for X-linked lissencephaly with abnormal genitalia. The brain of Arx knockout mice shows aberrant tangential migration and differentiation of gamma-aminobutyric acid (GABA)ergic interneurons. In human X-linked lissencephaly with abnormal genitalia, a neuropathologic study has suggested a loss of interneurons. Meanwhile, polyalanine expansion of ARX causes symptomatic or nonsymptomatic West's syndrome and nonsyndromic mental retardation. The striking epileptogenicity of X-linked lissencephaly with abnormal genitalia and West's syndrome associated with ARX mutations i s considered to be caused by a disorder of interneurons involving a tangentialmigration disorder. We propose "interneuronopathy" as a term for this.
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PMID:X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term, "interneuronopathy". 1592 Dec 44

Severe Myoclonic Epilepsy in infancy (SMEI, or Dravet syndrome) is a drug-resistant epilepsy that occurs in the first year of life of previously healthy children. The main clinical features are prolonged and repeated febrile and afebrile generalized or unilateral convulsive seizures. In the course of the epilepsy, cognitive deterioration becomes evident, and interictal myoclonus, clumsiness and ataxia appear. One third of the children with SMEI show de novo mutations of the SCN1A gene, and additional familial genes probably contribute to the phenotype. While the clinical picture of SMEI has been well studied, neuropsychological data remain scarce. Global mental retardation, attention deficit and psychotic behavior have been reported but the long-term outcome has not been evaluated. We conducted a longitudinal neuropsychological study of children with SMEI. Twenty children, aged 11 months to 16 years, were prospectively examined using standardized neuropsychological tests. Correlation analysis with other clinical features was performed in 12 cases. Marked slowing or stagnation of psychomotor development, accompanied by psychotic or autistic traits and hyperactivity, was observed between the ages of one and four years. In the later stages (at ages 5 to 16 years), cognitive function stabilized but remained below normal. In children with a more favorable course, language capacities were better preserved than visuospatial functions, and behavior improved. The cognitive and behavioral impairment tended to correlate with the frequency of convulsive seizures (>5 per month). The data suggest that SMEI can be considered as a prototype of an epileptic encephalopathy.
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PMID:Severe myoclonic epilepsy of infants (Dravet syndrome): natural history and neuropsychological findings. 1710 60


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