Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a 16-year-old Japanese girl with a mitochondrial encephalomyopathy who presented with progressive dementia, limb weakness and atrophy, episodic vomiting, generalized convulsions, myoclonic seizures, and hypertrophic cardiomyopathy. CT scan revealed transient focal low density areas in her occipital and parietal lobes, and cerebellar atrophy. The clinical features were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Microscopically, most of muscle fibers in the skeletal muscles and heart were occupied by markedly increased mitochondria. Polarographic studies on mitochondria isolated from postmortem heart muscle showed severe impairment of oxidation of NADH-linked substrates in contrast to normal succinate oxidation. The rotenone-sensitive NADH-coenzyme Q reductase activity was markedly decreased in heart, skeletal muscle and liver mitochondria. The biochemical investigations have led to the identification of a defect of complex I in the respiratory chain. Reported cases of a defect of complex I have revealed pure myopathy, encephalopathy or encephalomyopathy. The reason for a varied clinical expression of a single defect remains to be clarified.
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PMID:A mitochondrial encephalomyopathy with cardiomyopathy. A case revealing a defect of complex I in the respiratory chain. 310 81

We have studied a 17-year-old girl with lactic acidosis (3-18 mEq/liter) and progressive muscle weakness since 9 years of age. Morphological findings in muscle were of a typical ragged red myopathy with multiple collections of bizarre mitochondria, some containing paracrystalline inclusions. The carnitine content of serum and muscle was normal, as were the activities of carnitine palmitoyltransferase, carnitine octanoyltransferase, and carnitine acetyltransferase in the patient's muscle. Measurement of the enzymes of oxidative phosphorylation in both crude muscle homogenates and mitochondrial fractions showed close to normal activities of cytochrome c oxidase, succinate dehydrogenase, and ATPase. In contrast, succinate cytochrome c reductase activity was greatly reduced in the patient, being 0.035 mumol/min/g tissue in whole muscle (controls 1.16 +/- 0.47 mumol/min/g tissue) and 8 nmol/min/mg protein in the mitochondria (control, 340 nmol/min/mg protein). Rotenonesensitive NADH-cytochrome c reductase was also undetectable in the patient's mitochondria. Spectral analysis of cytochromes showed decrease of reducible cytochrome b to 16% of the control. These results indicate a defect of ubiquinol-cytochrome c reductase or the cytochrome bc1 segment (complex III) of the electron transport chain. Antibody-binding studies of the individual components of complex III showed additional deficiencies of core proteins I and II and peptide VI, indicating a more widespread defect of complex III than was evident from spectral analysis and enzyme activity measurements alone. Urine organic acid analysis after fasting and following a medium chain triglyceride load showed unusually high levels of lactate and 3-hydroxybutyrate, lower than expected levels of acetoacetate and dicarboxylic acids, and the presence of several other metabolites suggesting a disturbed citric acid cycle and redox state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lactic acidosis and mitochondrial myopathy associated with deficiency of several components of complex III of the respiratory chain. 609 35

The muscles of four infants with cerebro-hepato-renal (Zellweger) syndrome were studied during life and/or at necropsy. A mitochondrial myopathy was demonstrated, similar to mitochondrial alterations demonstrated in liver and brain in this disease. Muscle fibers with red-staining subsarcolemmal aggregates were identified with Gomori trichrome stain in two cases. Subsarcolemmal and intermyofibrillar zones of increased concentrations of NADH-TR, SDH, and cytochrome-c-oxidase activity were demonstrated histochemically in all four cases. Degenerative and cytoarchitectural changes in muscle fibers were not found. Ultrastructural studies showed large aggregates of mitochondria and increased lipid in the subsarcolemmal and intermyofibrillar spaces. Degenerative changes in mitochondria and lipid also were demonstrated, but paracrystalline inclusions were not seen. The distribution of these changes was not uniform between patients or between different muscles in the same patient. The diaphragm was affected more severely than proximal or distal muscles of the extremities. Direct involvement of muscle mitochondria in this disease may interfere with energy metabolism and contribute to the clinical findings of hypotonia, weakness, and respiratory insufficiency. The muscle biopsy with histochemistry and electron microscopy may be used as a diagnostic adjunct in suspected cases, but the variation encountered dictates dictates caution in the interpretation of negative findings.
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PMID:Mitochondrial myopathy of cerebro-hepato-renal (Zellweger) syndrome. 661 47

This paper presents biochemical data upon a young male with a mitochondrial myopathy characterised by weakness, severe exercise intolerance, muscle wasting and exercise-induced lactic acidaemia. Two similar cases have been previously documented (Morgan-Hughes et al. 1979). This report more precisely locates the mitochondrial defect. In vitro mitochondrial studies show markedly decreased respiratory rates with all NAD-linked substrates whilst that with flavin-linked succinate is normal. Oxidative phosphorylation is normally coupled. Mitochondrial cytochrome components as determined by low temperature spectroscopy are normal. NADH-ferricyanide reductase and primary dehydrogenase activities are present at levels far in excess of that required to support normal NAD-linked substrate oxidation rates. Intramitochondrial NAD levels are similar to those found in other mammalian muscle. It is proposed therefore that the mitochondrial defect is situated between NADH dehydrogenase and the CoQ--Cytochrome b complex; possibly being a derangement of a non-haem iron sulphur centre.
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PMID:Mitochondrial myopathy. Biochemical studies revealing a deficiency of NADH--cytochrome b reductase activity. 722 53

In most of the cases previously described, the defect on complex II was suggested by low activity of succinate cytochrome C reductase (SCCR). The clinical pattern of the previous 10 cases is heterogeneous and may be limited to one particular tissue or be of a more general nature. We report a 22-year-old-woman, daughter of consanguineous parents, with generalized muscle weakness, easy fatigability and benign course, who showed a decrease of SCCR activity in mitochondria of muscle fibers. Free carnitine (FC) concentration was decreased in muscle as well. The muscle biopsy showed a mild variation in fiber size, with fiber type I predominance, subsarcolemmal oxidative DPNH accumulations, excess of neutral lipids and abnormally large mitochondria with paracrystalline inclusions. A possible inheritance pattern is discussed. Coenzyme Q10 therapy in this patient induced a significant increase of global MRC index score and a decrease of the turns-mean amplitude ratio in the automatic analysis of the EMG.
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PMID:Benign mitochondrial myopathy with decreased succinate cytochrome C reductase activity. 783 16

A 42-year-old female complained of exertional dyspnea and sleep disturbance. Her face was elongated longitudinally and the hard palate was narrow and high-arched. She has slender musculature and kyphoscoliosis. She was dysphonic and could not walk on her heels. Muscles in the face, upper arm, pelvic girdle and thigh were atrophic. Muscle weakness was detected in the neck, tibialis anterior, ilipsoas and other hip muscles, and ranged between 3- and 4 by the manual muscle testing. Electromyography showed definite myogenic abnormalities in all the muscle examined. No abnormality was found on the routine examination of blood, as was the motor and sensory nerve conduction velocity. Her vital capacity was 0.91 L, i.e., 35% of the expected value, suggesting a severe restrictive respiration. The arterial blood gas analysis revealed hypoxia, hypercapnia and desaturation. The blood gas data worsened when she was asleep, because of increased hypoventilation. Muscle biopsy of the biceps brachii showed a marked variation in the muscle fiber size. The type 1 muscle fiber was predominant. Many fibers contained nemaline rods and/or core-like structures. Some fibers contained both nemaline and core-like structures. This core-like structures were not stained with NADH-TR and ATPase reactions, and about 40-100 microns in the longitudinal extension. In this context, typical central cores have not been observed in the present case. No association of nemaline rods and core-like structures in the same muscle fiber has been reported, although a close relationship of the two structures has been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An adult case of congenital myopathy--coexistence of nemaline rods and core-like structures]. 815 9

Multicore myopathy is a rare congenital myopathy. The multicores consist of numerous small areas of decreased oxidative enzyme activity. The long axis of the lesion is perpendicular or parallel to the long axis of the muscle fiber. These cores are usually smaller than central cores. For this reason they are also called minicores. Although the multicores represent a nonspecific change in that they can be observed in malignant hyperthermia, muscular dystrophy, inflammatory myopathy, etc. Muscular weakness dating from early infancy is combined large proportion of the muscle fibers. In about half of the reported cases the muscular weakness has not been progressive, while in the others a slow progression has occurred. This 9-year-old boy presented with congenital nonprogressive myopathy associated with thoracic scoliosis and bilateral equinovarus deformity. The serum creatine phosphokinase and lactic dehydrogenase levels were normal. Electromyography showed "myopathic" features. The biopsy revealed a marked size variation in myofibers, ranging from 10 microns to 100 microns. A few small angular fibers and slight endomyseal fibrosis were also noted. There was type I fiber predominance. NADH-TR reaction disclosed more well-defined cores with loss of intermyofibrillary mitochondrial activity. These cores were usually located with loss of intermyofibrillary mitochondrial activity. These cores were usually located in the peripheral portions of the myofibers and the core size measured 10-30 microns in diameter. Electron microscopic examination revealed circumscribed areas of disintegrated Z band material and disorganized sarcomeric units near the sarcolemma. A decrease in the number of mitochondria and glycogen particles was noted.
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PMID:Multicore myopathy--a case report. 819 69

Vitamin E deficiency in rats gives rise to a neuromuscular syndrome that includes a peripheral neuropathy as well as generalised muscle wasting and weakness. This is probably related to damage by oxygen-derived free radicals. In the present study, histological examination of lower limb muscles showed widespread myopathic changes which included the presence of amorphous electron-dense inclusions and tubular aggregates in muscle fibres and muscle fibre necrosis. Histochemical observations suggested a reduction in the activity of oxidative enzymes. The mitochondria showed nonspecific degenerative changes on electron microscopy; no paracrystalline inclusions were observed. Polarographic analysis of isolated muscle mitochondria revealed statistically significant decreases in oxygen utilisation rates with both NADH and FADH2-linked substrates. In confirmation of a generalised respiratory chain abnormality, enzymatic analyses revealed decreases in the activities of complexes I, II/III and IV, although only the decreases in complexes I and IV activities were statistically significant. Measurements of membrane fluidity showed that this is reduced in mitochondria from vitamin E deficient rats, indicating reduced stability of their membranes. The respiratory control ratio, derived from the polarographic results, was also reduced in mitochondria from vitamin E deficient animals, suggesting membrane damage. An altered lipid environment, possibly secondary to a higher level of lipid peroxidation, could result in the inhibition of complexes I and IV. This could also be caused by oxidative damage to the complexes or to mitochondrial DNA. The preservation of citrate synthase activity is against any generalised defect of mitochondrial function. The question as to whether these defects of mitochondrial respiratory chain function are responsible for the muscle fibre damage and necrosis requires further investigation.
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PMID:Myopathy in vitamin E deficient rats: muscle fibre necrosis associated with disturbances of mitochondrial function. 830 Apr 27

The authors report the case of a female patient, 18 years of age, with slowly progressing weakness in upper and lower limbs since childhood. There were no significant antecedents. The neurologic examination showed mild proximal and distal motor deficit with a slight muscular retraction at the level of shoulders, elbows, coxofemural joints, knees and ankles; muscular hypotrophy in the legs and feet; reflexes were present and sensitivity was normal. Creatinephosphokinase showed an increase of one and a half times the normal value. Electroneuromyography: decrease in the amplitude and duration of action potentials and excessive recruitment of motor units, compatible with a primary muscular disease. A muscle biopsy with frozen sections (HE, Gomori, PAS, ATPases, NADH, SDH, acid and alcaline phosphatases, cytochrome oxidase and Oil-red-o) revealed a primary muscular disease characterized by the presence of nemalinic and intracytoplasmic spheroid bodies. Nemalinic bodies have been described with different structural abnormalities of muscle fibers; however, such association is rare. This is the second case report of concomitant occurrence of nemalinic and spheroid bodies.
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PMID:[Nemalinic myopathy with intracytoplasmic spheroid bodies: report of a case]. 873 55

A 32 year old woman with a history of anorexia nervosa began experiencing severe muscle weakness. Proximal weakness was worse than distal and she became unable to walk. Serum creatine kinase was elevated 15-fold and EMG was consistent with a myopathic process. Muscle biopsy showed focal areas of absent staining using NADH and ATPase enzyme histochemistry. Gomori trichrome revealed many positive inclusions which were positive using immunohistochemistry for actin. Electron microscopy revealed these areas to contain cytoid bodies with Z-band streaming and disorganization of the myofibrillar network. These findings are consistent with the myopathy associated with ipecac (emetine) toxicity. A urine toxicology screen demonstrated evidence of emetine abuse, which was later admitted by the patient. Following discontinuation of the drug, the patient recovered normal muscle strength.
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PMID:Case of the month. June 1996--anorexia nervosa. 894 26


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