Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A thirty-two year old female had chronic progressive external ophthalmoplegia (CPEO), exertional fatigue, dysarthria, dysphagia, and bilateral hearing impairment. Histochemical stains, obtained from the right vastus lateralis, showed ragged-red fibers and wide-spread abnormalities in the number, size, and the structure of mitochondria under electronomicroscopic examination. A biochemical analysis showed a low activity of NADH-cytochrome C reductase, NADH dehydrogenase and a normal activity of succinate cytochrome C reductase and cytochrome C oxidase. This data suggests a specific defect in the NADH dehydrogenase of complex I (NADH CoQ reductase). We believe that this is the first biochemically defined mitochondrial myopathy reported in Taiwan and provides additional evidence for the existence of biochemical heterogeneity in mitochondrial disorders of CPEO.
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PMID:Chronic progressive external ophthalmoplegia with NADH-CoQ reductase deficiency: report of a case. 132 93

We describe a 53-year-old patient with a progressive mitochondrial myopathy of late-onset, restricted to skeletal muscle only without external ophthalmoplegia. The myopathy developed at the age of 46 years initially with exercise intolerance and subsequently progressive permanent muscle weakness. Muscle biopsy revealed severe myopathic changes, ragged red fibers, and a marked multifocal cytochrome-c-oxidase deficiency. Biochemical analysis showed a deficiency of complexes I and IV of the mitochondrial respiratory chain. Genetic analysis of mitochondrial DNA revealed no deletions. Mitochondrial myopathies restricted to skeletal muscle have to be considered in the differential diagnosis of late-onset progressive myopathies.
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PMID:[Delayed manifestation of mitochondrial myopathy--complex I and IV deficiency of the mitochondrial respiratory chain with progressive paresis]. 165 69

Biochemical and histochemical studies were carried out on 2 patients with chronic progressive external ophthalmoplegia (CPEO). Histological examination revealed prominent ragged-red fibres in the Gomori trichrome stain and cytochrome oxidase staining revealed partial depletion of cytochrome oxidase with negative staining in some fibres with prominent subsarcolemmal mitochondrial aggregations. Polarographic studies with isolated intact skeletal muscle mitochondria revealed low State III respiration rates with NAD- and FAD-linked substrates. Cytochrome aa3 levels were depressed in the one case where a cytochrome difference spectra was recorded. Cytochrome oxidase levels were greatly depressed in muscle homogenate, whereas monoamine oxidase levels were in the normal range, indicating a selective depletion of the former enzyme complex. It is possible that deficiency of cytochrome oxidase may arise as an epiphenomenon in degenerating mitochondria rather than a primary deficiency.
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PMID:Partial cytochrome oxidase (aa3) deficiency in chronic progressive external ophthalmoplegia. Histochemical and biochemical studies. 241 59

A 42-year-old woman had a 10-year history of external ophthalmoplegia, malabsorption resulting in chronic malnutrition, muscle atrophy and polyneuropathy. Computer tomography revealed hypodensity of her cerebral white matter. A metabolic disturbance consisted of lactic acidosis after moderate glucose loads with increased excretion of hydroxybutyric and fumaric acids. Post-mortem studies revealed gastrointestinal scleroderma as the morphological manifestation of her malabsorption syndrome, ocular and skeletal myopathy with ragged red fibers, peripheral neuropathy, vascular abnormalities of meningeal and peripheral nerve vessels. Biochemical examination of the liver and muscle tissues revealed a partial defect of cytochrome-c-oxidase (complex IV of the respiratory chain). This mitochondrial multisystem disorder may represent a separate entity to be classified between the spectrum of myoencephalopathies and oculo-gastrointestinal muscular dystrophy.
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PMID:Myo-, neuro-, gastrointestinal encephalopathy (MNGIE syndrome) due to partial deficiency of cytochrome-c-oxidase. A new mitochondrial multisystem disorder. 282 22

We studied skeletal muscles from eight chronic progressive external ophthalmoplegia patients with ragged-red fibers (group A), five CPEO patients without ragged-red fibers (group B), and five controls. The EM morphometric fraction of structurally abnormal mitochondria was increased in group A, and there was a similarly increased fraction of normal-appearing mitochondria in group B. State 3 respiration and uncoupled respiration were severely decreased in both groups. The morphometric mitochondrial fraction and respiratory functions were inversely related in all three groups. The cytochrome content in group A was normal; cytochromes b and cc1 were decreased in group B. These studies point to a central role of mitochondrial dysfunction in all types of CPEO, but the basic abnormalities remain to be elucidated.
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PMID:Chronic progressive external ophthalmoplegia (CPEO): clinical, morphologic, and biochemical studies. 630 Jul 33

Fatal infantile mitochondrial myopathy with lactic acidosis, morphologically abnormal mitochondria, deficient cytochromes aa3 and b, and a Fanconi-like aminoaciduria has been described. We report two infants, second cousins, with a similar fatal mitochondrial disorder, the cytochrome deficiency limited to skeletal muscle in one child and to liver in the other. The first child at 3 months of age had weight loss, hypotonia, external ophthalmoplegia, and a severe lactic acidosis with a high lactate/pyruvate ratio. Electron microscopy of muscle showed marked proliferation of enlarged mitochondria, many containing concentric rings of cristae. In skeletal muscle mitochondria, cytochromes aa3 and b were not detectable but cytochrome cc was found to be normal by spectroscopy. Cytochrome c oxidase activity was less than 1% of normal. Mitochondria from kidney, liver, heart, lung, and brain examined postmortem had normal cytochromes and preserved cytochrome c oxidase activity. The second cousin at 5 months of age had weight loss and hepatomegaly but no systemic lactic acidosis. Liver biopsy showed hepatocytes packed with enlarged mitochondria. The liver mitochondria showed deficient cytochromes aa3 and b postmortem, and cytochrome c oxidase activity was less than 10% of normal. Kidney mitochondria had normal cytochromes. Muscles was not studied. The mitochondrial abnormality in the two cousins presumably is related. Unexplained are the mode of genetic transmission or environmental exposure and the apparent involvement of a single different organ in each child.
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PMID:Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin. 631 75

In skeletal muscle biopsies of 8 patients with progressive external ophthalmoplegia combined light and fine structural cytochemical studies of cytochrome-c-oxidase revealed the absence of the enzyme in single fibres with or without accumulation of abnormal mitochondria. However, some fibres showed abnormal mitochondria without any deficiency of the enzyme. In one case with only slight mitochondrial proliferation the existence of the enzyme defect was the most remarkable finding. The occurrence of the enzyme defect obviously does not depend on concomitant structural alterations of the chondriom. The results are consistent with an acquired mitochondrial injury leading to a gradual loss of enzyme activity either earlier (with or without a minimal reactive mitochondrial proliferation) or later (after a phase of mitochondrial proliferation) in the course of the disease. Focal lack of cytochrome-c-oxidase activity is apparently a constant feature of the syndrome; it therefore may be not only of pathogenetic but also of diagnostic importance and in this connection cytochemical-fine-structural demonstration of cytochrome-c-oxidase is a valuable method. In contrast to the biochemical approach it allows not only the detection but also the exact anatomical localization of single fibre defects.
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PMID:Focal deficiency of cytochrome-c-oxidase in skeletal muscle of patients with progressive external ophthalmoplegia. Cytochemical-fine-structural study. 631 26

In muscle, the neural cell adhesion molecule (NCAM) is known to be expressed in denervated and regenerating fibers. Our present study, performed with immunohistochemical detection procedures, attempts to demonstrate the expression of NCAM in mitochondrial myopathy. Biopsy specimens from 29 patients were investigated. The following conditions were represented: nonweak control subjects (8 cases), chronic progressive external ophthalmoplegia (7 cases), Kearns-Sayre syndrome (5 cases), unclassified mitochondrial myopathy (2 cases), idiopathic polymyositis (7 cases). We demonstrate the expression of NCAM in mitochondrial myopathy. But NCAM is expressed in ragged-red fibers both in mitochondrial and idiopathic inflammatory myopathy. Furthermore, NCAM-immunoreactive fibers are more abundant than ragged-red and cytochrome-c-deficient fibers. Thus, we conclude that NCAM expression precedes histochemical and enzyme-histochemical demonstrable mitochondrial abnormalities. NCAM expression may reflect compensatory regenerating tendency of ragged-red fibers. Vimentin expression in mitochondrial myopathy favors this view. Probably, NCAM plays a role in the enrichment of abnormal mitochondria as a compensatory process for the biochemical deficit. The expression of NCAM in mitochondrial myopathies suggests that NCAM is related to the pathophysiology of these diseases and can be a helpful clue in the diagnosis of mitochondrial myopathy. But NCAM expression is not a specific phenomenon in mitochondrial myopathy, because in secondary mitochondrial changes like in idiopathic polymyositis NCAM expression is observed, too.
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PMID:Expression of NCAM (neural cell adhesion molecule) in mitochondrial myopathy. 860 39

To estimate the oxidative damage to skeletal muscle DNA in mitochondrial encephalomyopathies, we studied the amount of 8-hydroxy-deoxyguanosine (8-OH-dG) and the localization of superoxide dismutase (SOD) in the skeletal muscles of patients with progressive external ophthalmoplegia (PEO) or Kearns-Sayre syndrome (KSS). The molar ratio of 8-OH-dG/deoxyguanosine in skeletal muscle from PEO or KSS patients was significantly higher than the control value. The ratio from patients with polymyositis or Duchenne's muscular dystrophy was not significantly elevated. Immunohistochemical staining for both Mn-SOD and Cu,Zn-SOD showed pronounced staining in the subsarcolemmal and intermyofibrillar regions of cytochrome-oxidase-negative ragged red fibers of KSS or PEO muscles. Our findings suggest that overproduction of 8-OH-dG and mitochondrial dysfunction with gene deletions are associated with each other in muscle cells of patients with PEO or KSS, and that free radicals may play an important role in the pathophysiology of mitochondrial encephalomyopathies.
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PMID:Oxidative damage to skeletal muscle DNA from patients with mitochondrial encephalomyopathies. 883 81

To clarify the importance of deleted protein and tRNA genes on the impairment of mitochondrial function, we performed a quantitative analysis of biochemical, genetic and morphological findings in skeletal muscles of 16 patients with single deletions and 5 patients with multiple deletions of mtDNA. Clinically, all patients showed chronic progressive external ophthalmoplegia (CPEO). The size of deletions varied between 2.5 and 9 kb, and heteroplasmy between 31% and 94%. In patients with single deletions, the citrate synthase (CS) activity was nearly doubled. Decreased ratios of pyruvate- and succinate-dependent respiration were detected in fibers of all patients in comparison to controls. Inverse and linear correlations without thresholds were established between heteroplasmy and (i) CS referenced activities of the complexes of respiratory chain, (ii) CS referenced maximal respiratory rates, (iii) and cytochrome-c-oxidase (COX) negative fibers. In patients with single and multiple deletions, all respiratory chain complexes as well as the respiratory rates were decreased to a similar extent. All changes detected in patients with single deletions were independent of deletion size. In one patient, only genes of ND5, ND4L as well as tRNA(Leu(CUN)), tRNA(Ser(AGY)), and tRNA(His) were deleted. The pronounced decrease in COX activity in this patient points to the high pathological impact of these missing tRNA genes. The activity of nuclear encoded SDH was also significantly decreased in patients, but to a lesser extent. This is an indication of secondary disturbances of mitochondria at CPEO. In conclusion, we have shown that different deletions cause mitochondrial impairments of the same phenotype correlating with heteroplasmy. The missing threshold at the level of mitochondrial function seems to be characteristic for large-scale deletions were tRNA and protein genes are deleted.
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PMID:Mitochondrial respiratory rates and activities of respiratory chain complexes correlate linearly with heteroplasmy of deleted mtDNA without threshold and independently of deletion size. 1235 Dec 17


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