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)

Clinical findings were compared with the results of molecular analysis in 16 Japanese patients from 10 unrelated families with the adult/chronic form of GM1 gangliosidosis. Age of onset ranged from 3 to 30 years. Major clinical manifestations were gait and speech disturbances caused by persistent muscle hypertonia. Dystonic postures and movements, facial grimacing, and parkinsonian manifestations were commonly seen. Cerebellar signs, myoclonus, severe intellectual impairment, dysmorphism, or visceromegaly were not observed. A common single-base substitution, 51Ile(ATC)----Thr(ACC), reported in a previous study of ours, was confirmed in 14 patients by the Bsu36I restriction site analysis; one was a compound heterozygote with another mutation (457Arg[CGA]----Gln[CAA]) and the others were homozygotes of this mutation. Clinically, the compound-heterozygous patient showed more severe neurological manifestations and a more rapid clinical course than those of homozygotes. The homozygotes showed considerable variations in the age of onset and subsequent clinical course. The 51Ile----Thr mutant allele expressed a significant amount of beta-galactosidase activity, whereas the 457Arg----Gln mutant allele expressed extremely low activity in human GM1 gangliosidosis fibroblasts. We conclude that these gene mutations causing different residual enzyme activities are related to the severity of clinical manifestations, but some other genetic or environmental factors contribute to clinical heterogeneity. The Bsu36I restriction site analysis was performed in 7 families and provided clear results for the diagnosis of heterozygotes as well as homozygotes of this specific clinical form of GM1 gangliosidosis. The technique is applicable to prenatal diagnosis and genetic counseling.
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PMID:GM1 gangliosidosis in adults: clinical and molecular analysis of 16 Japanese patients. 135 43

We report on 2 unrelated Japanese families, each with several individuals affected with hyperekplexia, a rare autosomal dominant form of exaggerated startle response of neonatal onset. In the first family, affected relatives included a 4-week-old boy, his mother, grandmother, a maternal uncle, and 2 maternal cousins. In the second family, affected were a 4-week-old boy, his father, and an elder brother. These 9 individuals had various combinations of transient infantile hypertonia and hypokinesia, exaggerated startle response with falling episodes, nocturnal myoclonus and an easily elicited head retraction reflex, hip dislocation, and umbilical hernia. Treatment with clonazepam was effective in relieving these manifestations in the affected infants and children. Genetic analysis of these 2 families and 4 others in the literature suggests autosomal dominant inheritance with considerable variability but complete penetrance. Another 3 families in the literature were reported, suggesting the existence of startle disorder with an autosomal recessive inheritance. A sporadic case is also known, presumably representing a fresh mutation of a dominantly inherited trait.
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PMID:Hyperekplexia: pedigree studies in two families. 189 65

Startle disease is an autosomal dominant disorder with two phenotypic expressions. In the major form, there is hypertonia in infancy, and later an insecure gait. The patients have falling attacks without unconsciousness and in these, they are often injured or suffer concussions. Episodes of shaking of the limbs lasting for several minutes and resembling generalized clonus or repetitive myoclonus occur. These are most often nocturnal and are also unaccompanied by loss of consciousness. the patients are hyperreflexic and show an increased incidence of associated neurological and electroencephalographic abnormalities. The minor form of startle disease is only manifested by excessive startle and this is inconstant. In infancy it is brought out by febrile illness and in adult life by emotional stress. Gastaut and Villeneuve postulated the existence of a sporadic form of hyperekplexia different from the disorder described by Suhren et al. Review of their report and comparison with the cases of Suhren et al, and our own patients leads us to believe that the sporadic and familial forms of startle disease are the same. The disorder is rare, probably misdiagnosed initially as spastic quadriplegia, and later as epilepsy. Clonazepam appears to be the treatment of choice and its effect is sustained.
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PMID:Startle disease or hyperekplexia: further delineation of the syndrome. 677 25

A case of acute hepatic failure following ingestion of the veterinary euthanasia drug T61 is described. Presenting symptoms were drowsiness, disorientation, muscle hypertonia, and upper limb myoclonus, which faded within a few hours. Two days later, acute liver failure occurred, manifested as encephalopathy, jaundice, and a severe coagulopathy. The hepatic damage was thought to be due to the solvent dimethylformamide, which is the only known hepatotoxin included in the preparation utilized in the suicide attempt. High-dose (1.2 g/day) intravenous reduced glutathione was administered, with a rapid improvement of liver function. The patient was discharged after 17 days. Normalization of all liver function tests was achieved within two months. The favorable outcome in this case stands in contrast to the report of a previous case of lethal T61-induced hepatic failure. Although a different amount of dimethylformamide was ingested in each case (0.45 vs 0.60 ml/kg body wt) and individual differences in susceptibility to the effects of the hepatotoxic agent may have played a major role in these two cases, it is not unlikely that the infusion of high doses of glutathione to our patient contributed to her survival and hepatic recovery.
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PMID:Severe hepatic failure occurring with T61 ingestion in an attempted suicide. Early recovery with the use of intravenous infusion of reduced glutathione. 846 75

The major form of familial hyperekplexia, a rare autosomal dominant disorder, is characterized by an abnormal startle reaction elicited by auditory and somatosensory stimuli, with transitory stiffness during the neontam period, followed later by falling attacks accompanied by momentary generalized muscular stiffness. Affected neonates occasionally have fatal hypertonia. The minor form is characterized only by an inconstant excessive startle response. We encountered a family in which three females presented with a partial or complete major form of the disease. All our patients were hyperreflexic, insecure gait was present in two subjects, without concomitant spontaneous nocturnal myoclonus. The pathophysiological basis of the hyperekplexia remains unclear. The abnormal startle reflex, probably related to the lack of inhibition by higher centers, is relayed in the caudal brainstem (ponto-medullary reticular formation), where bulbospinal motor efferents originate. Moreover, nonspecific changes such as large somatosensory evoked potentials and long-loop reflexes ("C-responses") may indicate increased cortical neuronal excitability. Polygraphic studies in these patients were normal. The locus of the major form of the disorder is located on chromosome 5q33-q35. Sequence analysis of the alpha 1 subunit of the inhibitory glycine receptor (GLRA1) revealed a mutation at the same codon 271 in several families (G1192A and G1192T). We analyzed this gene and found a G1192A mutation changing an ARG to a LEU codon in all three presented patients. Sporadic cases may represent new mutations or lack of penetrance in some family members. Only one of our three patients needed clonazepam. The diagnosis of this disorder rules out epilepsy, or psychogenic pathological startle reaction. Electrophysiological criteria are useful, however perinatal hypertonia or a tonic generalized spasm accompanied with falls following an abnormal startle reaction and genetic studies remain the diagnostic milestones of familial hyperekplexia.
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PMID:[Familial hyperekplexia: startle disease. Clinical, electrophysiological and genetic study of a family]. 894 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

We prospectively studied motor symptoms in 32 patients with CT- or MRI-proven acute pure parietal stroke. A transient, mild, 'pseudoparesis' of the hand (90%), was noted, improved by visual attention and prompting, associated with non-awareness of muscle power (53%), transient soft pyramidal signs (50%), unilateral akinesia (100%) and motor hemineglect (37%) in non-dominant lesions. Lower motoneurone-type atrophy was not observed in this acute phase. We called 'poikilotonia' the striking unpredictable variations in muscle tone, ranging from extreme hypertonia to hypotonia, found in all patients. When maintaining postures, patients showed large oscillations (100%), laterodeviation or levitation of the arm (60%), especially in the case of large or posterior lesions, or, occasionally (3%), motor persistence or even hemicatalepsy (3%). Limb kinetic and manipulatory apraxia, with inadequate organization and anticipation of motor sequences and synergies, motor arrests, perplexity, unrecognizable gestures and loss of bimanual coordination, was a constant finding (100%). Other apraxias (62%) and difficulty in copying intransitive gestures of the hand (84%) were associated with posterior lesions involving the supramarginal gyrus. When reaching towards objects, all patients showed abnormal anticipatory hand shaping, but visuomotor ataxia (3%) was only seen with bilateral posterior stroke. Sensory (70%) or pseudocerebellar (4%) ataxia, was seen in both anterior and posterior lesions. Avoidance behaviors (34%) were not uncommon, but had no localizing value. Of the dyskinesias, hand dystonia (84%) was frequent, but athetosis (16%), asterixis (15%), postural tremor (15%), myoclonus (9%) and stereotypia (9%), were uncommon. The abnormal eye movements were unilateral hypo-akinesia of exploratory saccades (43%), abnormal ipsilateral pursuit and contralateral optokinetic nystagmus in the case of posterior lesions, and oculomotor apraxia with bilateral posterior lesions. In conclusion, parietal motor syndrome can be recognized during bedside examination, and probably reflects the loss of multiple sensory feedback to motor programs, especially those directed to the extrapersonal space.
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PMID:Parietal motor syndrome: a clinical description in 32 patients in the acute phase of pure parietal strokes studied prospectively. 987 53

Tetrahydrobiopterin (BH4) deficiencies are a heterogeneous group of disorders caused by a defect in two of the three enzymes involved in its biosynthesis or in the two recycling enzymes. Except for the deficiency of dehydratase, an enzyme catalyzing a reaction in the recycling pathway, all other variants of BH4 deficiency are characterized by developmental delay, progressive neurological deterioration, hypokinesis, drooling, swallowing difficulty, truncal hypotonia, increased limb tone, myoclonus and brisk deep tendon reflexes. A deficiency of guanosine triphosphate cyclohydrolase I (GTPCH), the first enzyme in the biosynthetic pathway of BH4, is described in a 14-month-old male infant with hyperphenylalaninemia, developmental delay, hypertonia of the extremities, seizures, feeding difficulties, and vomiting. Urinary pteridine screening revealed very low levels of neopterin and biopterin which was highly suggestive of GTPCH deficiency. Low cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid concentrations, together with no detectable neopterin and decreased concentrations of biopterin and folate, agreed with the diagnosis of GTPCH deficiency. Subsequently measured neopterin and biopterin synthesis in cytokine-stimulated skin fibroblasts confirmed GTPCH deficiency, albeit indirectly. The patient showed marked improvement on a low-protein low-phenylalanine diet with neurotransmitter precursor administration. The favorable outcome in this patient clearly shows that not only newborns with elevated phenylalanine levels but also older children with neurological signs and symptoms should be screened for a BH4 deficiency in order to have maximum benefit of the treatment.
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PMID:Guanosine triphosphate cyclohydrolase I deficiency: a rare cause of hyperphenylalaninemia. 1077 Jun 63

Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by an exaggerated persistent startle reaction to unexpected auditory, somatosensory and visual stimuli, generalised muscular rigidity, and nocturnal myoclonus. The genetic basis is a mutation usually of the arginine residue 271 leading to neuronal hyperexcitability by impairing glycinergic inhibition. Hyperekplexia is usually familial, most often autosomal dominant with complete penetrance and variable expression. It can present in fetal life as abnormal intrauterine movements, or later at any time from the neonatal period to adulthood. Early manifestations include abnormal responses to unexpected auditory, visual, and somatosensory stimuli such as sustained tonic spasm, exaggerated startle response, and fetal posture with clenched fists and anxious stare. The tonic spasms may mimic generalised tonic seizures, leading to apnoea and death. Consistent generalised flexor spasm in response to tapping of the nasal bridge (without habituation) is the clinical hallmark of hyperekplexia. Electroencephalography may show fast spikes initially during the tonic spasms, followed by slowing of background activity with eventual flattening corresponding to the phase of apnoea bradycardia and cyanosis. Electromyography shows a characteristic almost permanent muscular activity with periods of electrical quietness. Nerve conduction velocity is normal. No specific computed tomography findings have been reported yet. Clonazepam, a gamma aminobutyric acid (GABA) receptor agonist, is the treatment of choice for hypertonia and apnoeic episodes. It, however, may not influence the degree of stiffness significantly. A simple manoeuvre like forced flexion of the head and legs towards the trunk is known to be life saving when prolonged stiffness impedes respiration.
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PMID:Hyperekplexia in neonates. 1152 14

A single case study of a 58 year-old male with right asymmetric apraxia and akinetic-rigid syndrome is described. Brainimaging scans (MRI, SPECT) indicated asymmetric cortical atrophy compatible with the diagnosis of Corticobasal Degeneration. Reflex myoclonus was absent and myoclonic discharges only appeared in response to pharmacological treatment of limb dystonia and rigidity. Electromyographic evidence of jerky movements was recorded only in the affected right hand and forearm after muscle relaxation, and myoclonus was not preceded by an EEG paroxysm. The cortical components of the correspondent SEPs were not increased in amplitude while LLRs recordings showed a late response over the muscles of the affected side. Furthermore, the duration of post MEP silent period was bilaterally reduced. This single case study report points out that sometimes myoclonus in Corticobasal Degeneration can be masked by the presence of increased muscle tone.
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PMID:Masked myoclonus in corticobasal degeneration: neurophysiological study of a case. 1185 Oct 11


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