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)

Intermittent, rhythmical myoclonus that had been present in the lower limbs of a 68-year-old man for more than 50 years was obviously increased in frequency during the period when the patients suffered from acute transverse myelitis. The same type of movements were readily induced by irrigation of the urinary bladder during the period of paraparesis. Removal of some possible inhibitory influences from a myoclonic focus in the lower spinal cord with resulting heightened excitability was thought to be the mechanism of these phenomena, although direct irritation of the myoclonic focus by the inflammatory process was also conceivable. The patient had keratosis palmoplantaris hereditaria and retinal pigment degeneration, suggesting the possibility of a congenital neuroectodermal dysplasia.
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PMID:Spinal myoclonus with dermal and retinal changes affected by myelitis. 14 Jun 43

We describe a patient with adult-onset neuronal storage disease characterized by myoclonus, cerebellar ataxia, convulsive seizures, cherry-red spots, skeletal dysplasia, mild gargoyle features, inguinal hernia, and angiokeratoma. Cytoplasmic inclusions consistent with lysosomal storage disease were demonstrated in neurons of the autonomic nervous system. Accumulation of GM3 and GM2 gangliosides was found in sympathetic ganglia but a catabolic disturbance of these gangliosides was ruled out by normal levels of GM3 ganglioside sialidase and N-acetyl-beta-hexosaminidase A activities. beta-Galactosidase activity was decreased in leukocytes and fibroblasts, but not in serum. GM1 gangliosidosis was ruled out by lipid analyses, and mucopolysaccharidosis by normal excretion of mucopolysaccharide in urine. Sialyl oligosaccharides were increased in urine and alpha-neuraminidase was deficient in fibroblasts. This disorder is considered to be an inherited metabolic disorder of sialyl glycoproteins and oligosaccharides due to deficiency of an alpha-neuraminidase.
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PMID:Adult type neuronal storage disease with neuraminidase deficiency. 53 22

Focal cortical myoclonus is rare. Obvious causes include tumor or atrophy involving the motor strip, but in some cases no cause is apparent. We present 4 patients who started to have focal myoclonus in childhood. All had focal motor seizures as well, and one had recurrent focal motor status epilepticus. All 4 had a mild progressive hemiparesis. Electrographic investigations showed focal epileptic discharges in the contralateral rolandic areas. Radiological studies were unrevealing, but magnetic resonance showed rolandic lesions in 3 patients. At surgery, abnormally wide gyri were found in the distribution demonstrated by magnetic resonance. The pathological substrate was focal cortical dysplasia. All patients have improved considerably following surgery. These findings suggest that focal myoclonus may be due to a rolandic neuronal migration disorder. Visualization of these lesions by magnetic resonance permits development of a surgical strategy leading to optimal treatment of these medically intractable epileptic disorders.
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PMID:Focal cortical myoclonus and rolandic cortical dysplasia: clarification by magnetic resonance imaging. 313 90

Sialidase (neuraminidase, EC 3.2.1.18) catalyses the hydrolysis of terminal sialic acid residues of glyconjugates. Sialidase has been well studied in viruses and bacteria where it destroys the sialic acid-containing receptors at the surface of host cells, and mobilizes bacterial nutrients. In mammals, three types of sialidases, lysosomal, plasma membrane and cytosolic, have been described. For lysosomal sialidase in humans, the primary genetic deficiency results in an autosomal recessive disease, sialidosis, associated with tissue accumulation and urinary excretion of sialylated oligosaccharides and glycolipids. Sialidosis includes two main clinical variants: late-onset, sialidosis type I, characterized by bilateral macular cherry-red spots and myoclonus, and infantile-onset, sialidosis type II, characterized by skeletal dysplasia, mental retardation and hepatosplenomegaly. We report the identification of human lysosomal sialidase cDNA, its cloning, sequencing and expression. Examination of six sialidosis patients revealed three mutations, one frameshift insertion and two missense. We mapped the lysosomal sialidase gene to human chromosome 6 (6p21.3), which is consistent with the previous chromosomal assignment of this gene in proximity to the HLA locus.
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PMID:Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis. 905 50

Sudden and brief involuntary movements of central nervous system (CNS) origin called myoclonus may be cortical (motor strip), thalamocortical (thalamocortical loop) or reticular (caudal reticular formation). Epileptic, cortical and thalamocortical myoclonus are combined with a spike which, when it is focal, needs back-averaging to be demonstrated. Negative myoclonus due to lapse of tone can only be demonstrated during antigravidic posture and may be combined with either a slow wave or the second, positive component of a polyspike-wave. Epileptic myoclonus must be distinguished from epileptic spasms and tonic seizures, and from non-epileptic myoclonus, tics, tremor and chorea. Myoclonus may occur in partial symptomatic (mainly Rasmussen and dysplasia), cryptogenic (frontal) or idiopathic (negative myoclonus in CSWS) epilepsy. Generalized myoclonus is part of inborn errors of metabolism, non-progressive encephalopathy (mainly Angelman) and idiopathic epilepsy (juvenile and infantile benign and severe forms, and myoclonic-astatic epilepsy). Carbamazepine, vigabatrin and eventually lamotrigine may worsen myoclonus whereas it may be improved by benzodiazepines, valproate, lamotrigine, zonisamide and piracetam according to etiology. Pathophysiology must take in account maturation processes, lesions and genetic predisposition. However, precise mechanisms remain unknown and only hypotheses can be proposed, that could clarify the age-related EEG and clinical expression of the various syndromes.
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PMID:Myoclonus and epilepsy in childhood: 1996 Royaumont meeting. 960 May 41

We report three male siblings born with fatal encephalopathy comprising microcephaly, myoclonus and muscle hypertonia. All three patients died during infancy. Postmortem examination on the brain revealed that all infants had neuronal loss in the cerebellar cortex, inferior olivary and pontine nuclei, which were more pronounced in the older subject than the younger ones. In addition, they were associated with polymicrogyria in the cerebral cortex of the insula, olivary and dentate nuclear dysplasia, and a hypoplastic corticospinal tract. The clinical and neuropathological findings in our cases were identical to those in fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microencephaly [Albrecht et al., Acta Neuropathol 1993;85:394-399], but an association of malformations suggests a new genetic factor in pathogenesis of olivopontocerebellar hypoplasia.
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PMID:Three siblings of fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microcephaly. 962 93

Sialidosis is an autosomal recessive disease caused by the genetic deficiency of lysosomal sialidase, which catalyzes the hydrolysis 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 have analyzed the genomic DNA from nine sialidosis patients of multiple ethnic origin in order to find mutations responsible for the enzyme deficiency. The activity of the identified variants was studied by transgenic expression. One patient had a frameshift mutation (G623delG deletion), which introduced a stop codon, truncating 113 amino acids. All others had missense mutations: G679G-->A (Gly227Arg), C893C-->T (Ala298Val), G203G-->T (Gly68Val), A544A-->G (Ser182Gly) C808C-->T (Leu270Phe) and G982G-->A (Gly328Ser). We have modeled the three-dimensional structure of sialidase based on the atomic coordinates of the homologous bacterial sialidases, located the positions of mutations and estimated their potential effect. This analysis showed that five mutations are clustered in one region on the surface of the sialidase molecule. These mutations dramatically reduce the enzyme activity and cause a rapid intralysosomal degradation of the expressed protein. We hypothesize that this region may be involved in the interface of sialidase binding with lysosomal cathepsin A and/or beta-galactosidase in their high-molecular-weight complex required for the expression of sialidase activity in the lysosome.
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PMID:Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex. 1076 32

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

The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1-4 years of age at times imitate epilepsy with myoclonic-astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs.
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PMID:Symptomatic epilepsies imitating idiopathic generalized epilepsies. 1630 80

We report a 31-year-old patient who suffered from the left foot motor seizure since 6 years of age. In addition to spontaneous seizures, the seizures tended to be triggered by somatosensory stimulus to the left foot. Recently, he developed irregular myoclonic jerks of the left foot. Neurologically, he had mild impairment of fine movements of the left foot, but otherwise no weakness or sensory disturbance was noted. Interictal spikes were frequently recorded at the vertex region, where ictal discharges also started during the video-EEG monitoring. Electrical stimulation of the left tibial nerve evoked giant cortical components of somatosensory evoked potentials and C-reflex. Magnetoencephalographic study of both interictal and jerk-locked averaged spikes located the equivalent current dipole of both activities at the left foot primary somatosensory cortex (SI), where 3 tesla MRI revealed a focal abnormality consistent with focal cortical dysplasia. The present non-invasive investigation suggests that focal cortical dysplasia at SI could manifest intrinsic, autonomous, epileptogenicity as well as extrinsic, stimulus-sensitive, hyperexcitability, which are clinically manifested as spontaneous seizures and cortical reflex myoclonus, respectively.
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PMID:[Focal cortical dysplasia at the primary somatosensory cortex could manifest both intractable partial epilepsy and cortical reflex myoclonus]. 1688 1


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