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)

The neuronal ceroid lipofuscinoses are a newly-recognized group of lysosomal storage disorders in which neurodegeneration predominates. The pathophysiological basis for this is unknown. In the current paper, we sought to determine whether neurons that lack the enzyme responsible for the infantile form of neuronal ceroid lipofuscinosis (INCL) display abnormalities in culture that could be related to the clinical disorder. Electrophysiological and fluorescent dye studies were performed using cortical neuronal cultures established from postnatal day 2 palmitoyl-protein thioesterase-1 (Ppt1) knockout mice. We found a 30% reduction in synaptic vesicle number per bouton that was progressive with time in culture as well as an elevation in lysosomal pH, whereas a number of passive and active membrane properties of the neurons were normal. The reduction in vesicle pool size was also reflected in a decrease in the frequency of miniature synaptic currents. The progressive and gradual decline in vesicle numbers and miniature event frequency we observed here may be an early indicator of synapse degeneration, in keeping with observations during competitive stimulation at the neuromuscular junction or age-related synapse elimination recently reported by others. PPT1 did not colocalize with synaptic vesicle or synapse markers, suggesting that lysosomal dysfunction leads indirectly to the synaptic abnormalities. We conclude that from an early age, neurons deficient in PPT1 enzyme activity display intrinsically abnormal properties that could potentially explain key features of the clinical disease, such as myoclonus and seizures.
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PMID:Progressively reduced synaptic vesicle pool size in cultured neurons derived from neuronal ceroid lipofuscinosis-1 knockout mice. 1624 38

The neuronal ceroid lipofuscinoses are a heterogeneous group of inherited degenerative disorders of the central nervous system. Cases of ceroid lipofuscinosis with cytoplasmic storage of granular osmiophilic deposits are associated with reduced activity of palmitoyl-protein thioesterase-1 (PPT-1) and mutations in CLN1, and occur from infancy to adulthood. We present clinical and diagnostic investigations in six children with variant late infantile neuronal ceroid lipofuscinosis and mutations in CLN1. The main clinical features at onset were behavioral disturbances and cognitive decline. Myoclonic jerks constituted the most prominent paroxysmal phenomenon. An electroencephalogram revealed the "vanishing" pattern described in infantile ceroid lipofuscinosis. Neurologic regression was associated with dramatic shrinkage of cortical structures, evident upon brain magnetic resonance imaging. Three unrelated children harboring the same homozygous mutation in CLN1 and a girl who carried a novel mutation resulting in skipping of multiple exons presented with a similar clinical phenotype. The most severe picture occurred in two siblings who carried a homozygous mutation predicting a prematurely truncated protein. Similar to the infantile form, the clinical evolution in this group of patients was characterized by an onset of severe neurologic impairment, peaking within a relatively short period of time, followed by a slower evolution of the disease.
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PMID:Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations. 1930 39