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)

Diagnosis of respiratory chain defects in cultured skin fibroblasts is a difficult diagnostic procedure. We investigated the feasibility of using survival of skin fibroblasts in culture medium with galactose as the major carbon source as a method of quickly diagnosing cell lines that were compromised in oxidative metabolism. We found that cells from patients with most forms of cytochrome oxidase deficiency, cells with complex I deficiency, cells with multiple respiratory chain defects and cells with severe pyruvate dehydrogenase (PDH) complex deficiency failed to survive when subcultured into galactose (5 mM) medium. Cells from patients with Lebers hereditary optic neuropathy (LHON), Kearns-Sayre syndrome (KSS), myoclonus-epilepsy-lactic acidosis-stroke (MELAS), the hepatic form of cytochrome oxidase deficiency, and mild PDH complex deficiency survived well in galactose (5 mM)-containing medium. This could be used as a rapid screening test for skin fibroblasts with major oxidative defects.
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PMID:Nonviability of cells with oxidative defects in galactose medium: a screening test for affected patient fibroblasts. 132 73

Point mutations of mitochondrial DNA have been described in the muscle of patients with syndromes of myoclonic epilepsy and ragged red fibres (MERRF) and of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). We have found the MERRF mutation in members of 6 British kindreds; 2 of these had unusual phenotypes but all index patients had myoclonus. The MELAS mutation was detected in 17 patients from 16 families, who had a wide range of clinical features that particularly affected the central nervous system; stroke-like episodes were observed in 10.3 patients with mitochondrial DNA mutations did not have ragged red fibres on muscle biopsy, generally considered to be the morphological hallmark of mitochondrial diseases. In all 6 patients with the MERRF mutation, and 10 of 11 with the MELAS mutation, the genetic defect was easily detected in blood cells as well as muscle (blood samples were not available in 6 patients with MELAS mutations in muscle). Molecular genetic analysis of blood samples represents an inexpensive and reliable screening test for mitochondrial encephalopathies, and use of such techniques could influence diagnosis and genetic counselling in patients with seizure disorders and young-onset stroke.
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PMID:Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples. 167 25

We have reported the clinical and autopsy findings in a case with generalized seizures, myoclonus, blindness and deafness which was accompanied by stroke-like episodes. This case was diagnosed as mitochondrial encephalomyopathy, lactic acidosis & stroke-like episodes (MELAS) from these findings. Solitary and continuous lesions of softening were distributed in both hemispheres, more severely in the frontal and occipital poles. These lesions did not correspond to a vascular supply. The pulvinar, lateral and medial geniculate body of the thalamus, cerebellar vermis and dentate nucleus had small lesions of softening. The cortical lesions occurred mainly in layer 4, and the most prominent lesions among them appeared cystic, involving the subcortical white matter, but nerve cells in layer 1 and 2 were preserved. Proliferation of small blood vessels was seen around the softening areas. Electron microscopy revealed increased mitochondria in endothelial cells of these vessels, abnormal dense bodies in skeletal muscle cells and tightly packed mitochondria in choroid plexus epithelial cells. Immunohistochemical study suggested that vimentin positive cells were seen around lesions and proliferated vessels are different from those seen in the intact tissues.
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PMID:[An autopsy case of generalized seizures, myoclonus, blindness and deafness]. 220 39

We reported a case of mitochondrial encephalomyopathy with repeated stroke-like episodes. A 33-year-old single male was admitted to our hospital because of stroke-like episodes with visual field defect, hemiplegia and convulsion repeated seven times for the past seven years. There were no abnormalities on the physical examination. He was hallucinative and perseverative and had mental deficiency. Muscle weakness and atrophy were not prominent, and generalized hyporeflexia were present without pathological reflexes. Myoclonus was not observed. Serum CK and blood gas analysis were normal (pH 7.398). Although blood levels of lactate and pyruvate were almost within normal limit, lactate was elevated by 20WATT-15 minutes exercises. On the contrary, the CSF levels of lactate and pyruvate were elevated markedly. CT of the brain revealed the presence of the low density areas in the right occipital and the left frontal lobes. Cranial 4 vessels studies were unremarkable. EEG showed the diffuse slowness with spike and wave complex. CT of the muscles were normal. A specimen obtained from the left biceps brachii muscle showed ragged-red fibers without obvious myogenic or neurogenic changes, and accumulations of abnormal mitochondria with paracrystalline inclusion bodies were observed by electron microscopy. However, mitochondrial abnormalities were not seen in the vessel walls in the biopsied muscle. Activities of complex I + III, II + III, IV in mitochondria were normal. Clinical features of this case were consistent with MELAS. However, this case showed no muscle weakness, short stature and lactic acidosis which characterize MELAS, and the onset of this case was later than those cases that were reported before.
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PMID:[A case of mitochondrial encephalomyopathy characterized by repeated stroke-like episodes]. 250 53

A 19-year-old woman with long-standing sensorineural deafness, bilateral cataracts and mild clumsiness, presented with acute focal edema in the left temperoparieto-occipital area which required surgical decompression as a life-saving measure. Investigation revealed a persistent lactic acidemia and evidence of many ragged red fibres in a skeletal muscle biopsy specimen, suggesting a diagnosis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. The patient developed two further stroke-like episodes over a short period. One sibling died at the age of 14 years with a progressive neurological illness characterised by seizures, bilateral optic atrophy, ataxia, myoclonus and progressive dementia. The diagnosis of MELAS syndrome should be considered in young people presenting with stroke-like episodes that fail to conform to a given vascular territory, particularly if they have long-standing minor neurological abnormalities or a family history of obscure early onset neurological disease. The different clinical pictures in the two affected siblings in this family suggest that MELAS syndrome is part of a spectrum of inherited mitochondrial cytopathies rather than a discrete disease entity.
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PMID:Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS): adolescent onset with severe cerebral edema. 339 2

We describe three patients with mitochondrial myopathy, dementia, loss of vision and hearing, seizure disorder with myoclonus, intermittent headaches of a vascular type, visual hallucinations, cerebellar dysfunction, and lactic acidosis. Muscle biopsies in all patients and liver biopsy in one revealed abnormal mitochondria. The disorder may be due to a deficiency of mitochondrial NADH-CoQ dehydrogenase.
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PMID:Mitochondrial myopathy and encephalopathy: three cases--a deficiency of NADH-CoQ dehydrogenase? 641 59

We describe 2 sibs (brother and sister) with myopathy, sideroblastic anemia, lactic acidosis, mental retardation, microcephaly, high palate, high philtrum, distichiasis, and micrognathia. Very low levels of cytochromes a, b, and c were detected in the patients' muscle mitochondria. Deposition of iron within the mitochondria of bone marrow erythroblasts was observed on electron microscopy. Irregular and enlarged mitochondria with paracrystalline inclusions were also seen on electron microscopy of the patients' muscle specimen. Examination of DNA from the affected sibs showed no deletions in the mitochondrial DNA nor the mutations identified in the syndromes of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) or myoclonus, and epilepsy associated with rugged-red fibers (MERRF). Since the parents were first cousins and 2 of 6 sibs (male and female) were affected, we suggest that the syndrome expressed by our patients represents a previously unknown autosomal recessive disorder that includes mitochondrial myopathy, lactic acidosis, and sideroblastic anemia.
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PMID:Myopathy, lactic acidosis, and sideroblastic anemia: a new syndrome. 772 39

A 16-year-old girl presented with early-onset cerebellar ataxia, myoclonus, elevated lactic acidosis and hypogonadotropic hypogonadism. Muscle biopsy specimens revealed fibres with a "ragged" appearance with increased mitochondria and lipid droplets. Biochemical investigation revealed a deficiency of complex bc1 (complex III) of the mitochondrial respiratory chain. Genetic analysis did not show either deletions or known mutations of mitochondrial DNA (mtDNA). Phosphorus magnetic resonance spectroscopy (31P-MRS) showed defective energy metabolism in brain and gastrocnemius muscle. A decreased phosphocreatine (PCr) content was found in the occipital lobes accompanied by normal inorganic phosphate (Pi) and cytosolic pH. These findings represented evidence of a high cytosolic adenosine diphosphate concentration and a relatively high rate of metabolism accompanied by a low phosphorylation potential. Muscle 31P-MRS showed a high Pi content at rest, abnormal exercise transfer pattern and a low rate of PCr post-exercise recovery. These findings suggested a deficit of mitochondrial function. Therapy with vitamins K3 and C normalized brain 31P-MRS indices, whereas it did not affect muscle bioenergetic metabolism. In this patient, the endocrinological disorder is putatively due to a mitochondrial cytopathy. Although an unknown mtDNA mutation cannot be ruled out, the genetic defect may lie in the nuclear genome.
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PMID:Early-onset cerebellar ataxia, myoclonus and hypogonadism in a case of mitochondrial complex III deficiency treated with vitamins K3 and C. 779 18

In the last 4 years much progress has been made in the understanding of mitochondrial disorders. Point-mutations, deletions and depletion of the mitochondrial genome are associated with disorders like Leber's disease, MERRF (Myoclonus Epilepsia with Ragged Red Fibers), MELAS (mitochondrial Myopathy, Encephalopathy, Lactic acidosis and Stroke-like episodes) and several others. Recently, mitochondrial dysfunctions have been also related to neurodegenerative disorders like Parkinson's disease and to aging. Since the brain depends mostly on mitochondrial energy supply, mitochondrial dysfunctions may affect the nervous system more severely than other tissues causing or worsening diseases and playing a role in the biological deterioration of aging. Furthermore, the mitochondrial energy supply is associated with the production of highly reactive oxygen species. Ninety-five percent of the molecular oxygen is metabolized within the mitochondria by the electron-transport chain so that mitochondria are highly exposed to oxidative stress which may damage selected neuronal populations. Oxygen radicals created during respiration induce mitochondrial dysfunction which accelerates the production of more deleterious species of oxygen. The latter step further increases mitochondrial malfunction, thus intensifying and perpetuating the cycle. These two mechanisms combined may lead to cell death in brain and other tissues with high metabolic rate. Therefore, in neurodegenerative disorders such as Parkinson's disease mitochondrial dysfunction and oxidative stress may cause or worsen the clinical features.
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PMID:Oxidative stress and mitochondrial dysfunction in neurodegeneration. 784 18

A 50-year-old woman with subacute dementia and brain atrophy on CT showed periodic synchronous discharge (PSD) on electroencephalogram (EEG) and myoclonus. She was initially suspected of suffering from Creutzfeldt-Jakob disease (CJD), but dramatically recovered over 5 months. Based on further investigations, the final diagnosis was mitochondrial encephalomyopathy with an A-to-G substitution at nucleotide position 3243 in mitochondrial DNA (mtDNA), commonly seen in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This case suggests that patients suspected of suffering from CJD should be evaluated for mitochondrial encephalomyopathy.
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PMID:A MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) mtDNA mutation that induces subacute dementia which mimicks Creutzfeldt-Jakob disease. 800 Jan 5


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