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)

Histochemical, biochemical and electromyographic studies were performed in a case of carnitine deficiency in serum and in muscle. Clinical features include proximal muscle weakness, predominant type I fiber impairment, excess of triglycerides and moderate glycogen accumulation in muscle. No abnormalities of palmityl CoA synthetase, carnitine palmityl transferase, carnitine acetyl transferase and lipase were evidenced. An interesting EMG decremental pattern was recorded. Correlations between electromyographic and biochemical findings are considered. A clinical improvement, a normal plasma carnitine level and a normal response at EMG repetitive stimulation were found after carnitine treatment.
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PMID:A case of lipid storage myopathy with carnitine deficiency. Biochemical and electromyographic correlations. 61 13

A 16-year-old boy with a two-year history of recurrent attacks of myalgia, muscle cramps without weakness, and myoglobinuria was shown to have a deficiency in muscle carnitine palmityltransferase. Serum concentrations of creatinine phosphokinase, serum glutamic oxalacetic transaminase, and aldolase were elevated. An electromyogram was consistent with a nonspecific myopathy as were microscopic and ultrastructural examinations of biopsied muscle. Venous lactic acid response to ischemic exercise was compatible with paroxysmal idiopathic myoglobinuria. Activities of muscle phosphorylase A and B, phosphofructokinase, muscle palmityl CoA synthetase, carnitine, and serum carnitine were normal as was the glycogen content. Activity of muscle carnitine palmityltransferase (2.7 microM/minute/mg protein), as measured by a spectrophotometric method and by radioactive assay, was significantly reduced when compared to normal control subjects (14.5 microM/minute/mg protein) and ischemic control subjects (13.8 microM/minute/mg protein). Muscle carnitine acetyltransferase (13.4 microM/minute/mg protein) was approximately 50% of normal control values (25.5 microM/minute/mg protein). This is the third reported case of myoglobinuria in a patient associated with a deficiency of muscle carnitine palmityltransferase activity.
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PMID:Recurrent myoglobinuria and muscle carnitine palmityltransferase deficiency. 87 82

Propionyl CoA carboxylase deficiency was found in a 7-month-old boy who presented with attacks of vomiting, anorexia, weight loss, weakness, and hypotonia. He failed to thrive and had generalized seizures. He had propionic acidemia and hyperglycinemia; these are the manifestations of the ketotic hyperglycinemia syndrome. However, ketonuria was not a consistent part of his clinical picture, and he had at least two episodes of acute overwhelming illness, the latter one fatal, in which ketones were never found in the urine. Large amounts of pyrrolidone carboxylic acid were found in body fluids.
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PMID:Hyperglycinemia and propionyl coA carboxylase deficiency and episodic severe illness without consistent ketosis. 113 51

A young girl presented with recurrent episodes of muscle weakness culminating in a severe attack of generalized muscle weakness. In the muscle mitochondria from the patient there was an abnormal pattern of intermediates of beta-oxidation with an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters, and 3-oxoacylcarnitines. There was low activity of long-chain 3-hydroxyacyl-CoA dehydrogenase in mitochondria from all tissues. The activity of long-chain 2-enoyl-CoA hydratase was low in muscle mitochondria and 3-oxoacyl-CoA thiolase activity measured with 3-oxohexadecanoyl-CoA as substrate was low in fibroblast, muscle, and cardiac mitochondria but only partial deficiency was present when the activity was measured with 3-oxooctanoyl-CoA. The activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase in fibroblasts from the patient's parents was intermediate between those of controls and the patient. The patient has a combined defect of the long-chain 3-hydroxyacyl-CoA dehydrogenase, long-chain 3-oxoacyl-CoA thiolase, and long-chain 2-enoyl-CoA hydratase which appears to be inherited in an autosomal recessive manner. This suggests there is a multifunctional enzyme catalyzing these activities in human mitochondria and that this enzyme is deficient in our patient.
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PMID:Combined enzyme defect of mitochondrial fatty acid oxidation. 140 Oct 59

Defects of complex I of the mitochondrial respiratory chain are important causes of neurological disease. We report studies that demonstrate a severe deficiency of complex I activity with less severe abnormalities of complexes III and IV (less than 5, 63, and 30% of control values, respectively) in a skeletal muscle mitochondrial fraction from a 22-yr-old female with weakness, lactic acidemia, and the deposition of intramuscular neutral lipid. The observation that lipid accumulates in this and other patients with complex I deficiency suggests impaired mitochondrial fatty acid oxidation. To investigate this mechanism we have shown impaired flux through beta-oxidation [( U-14C]hexadecanoate oxidation was 66% of control rate) and accumulation of specific acyl-CoA ester intermediates. The changes in fatty acid metabolism in complex I deficiency are secondary to the reduced state within the mitochondrial matrix with low NAD+/NADH ratios.
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PMID:Impaired mitochondrial beta-oxidation in a patient with an abnormality of the respiratory chain. Studies in skeletal muscle mitochondria. 215 51

Several clinical entities are associated with disorders of fatty acid oxidation or transfer across the inner mitochondrial membrane. Over 40 cases of the primary carnitine deficiency syndrome have been reported to date and various subtypes have been characterized. This represents a large clinical spectrum. The deficiency of carnitine in muscle is at the basis of a syndrome characterized by muscle weakness and lipid storage myopathy. The systemic form of carnitine deficiency is more generalized and includes recurrent episodes of hepatic encephalopathy as well as lipid storage in muscle, liver and heart. In one subtype, hypoglycemia upon fasting and cardiomyopathy are found. There are also several causes of secondary carnitine deficiency states which are either acquired or associated with inborn errors of metabolism (organic acidurias, defects of acyl-CoA dehydrogenases). Clinically, Carnitine palmitoyltransferase (CPT) deficiency is a rather homogeneous syndrome presenting with recurrent episodes of myoglobinuria provoked by fasting or prolonged exercise. The only exception is an infantile variety associated with severe hypoglycemia and hepatic CPT deficiency. Using malonyl-CoA, a specific inhibitor of CPT-I, we had suggestions in five adult patients with myoglobinuria that CPT-II is lacking in muscle, liver and platelets while CPT-I is above the control level. The enzyme abnormality seems partial and limited to CPT-II or to its binding to the inner mitochondrial membrane.
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PMID:Clinical varieties of carnitine and carnitine palmitoyltransferase deficiency. 355 20

The presentation and treatment of a central hypoventilation syndrome in a boy with pyruvate dehydrogenase complex (PDHC) deficiency are reported. Dephosphorylated PDHC was assayed in disrupted fibroblasts after pretreatment with dichloroacetate, a pyruvate dehydrogenase kinase inhibitor. Maximal specific activity of activated patient PDHC was 10% to 30% of control values. Patient PDHC activity was not increased by alterations in concentrations of pyruvate or cofactors (thiamine pyrophosphate [TPP], coenzyme A [CoA], oxidized form of nicotinamide adenine dinucleotide [NAD+]). Clinically, normalization of plasma lactate by a high-lipid diet did not prevent slowly progressive neurologic decline. The patient manifested intermittent ataxia, episodic profound weakness, moderate psychomotor retardation, ophthalmoplegia, and retinal pigment epithelial changes. A true central hypoventilation syndrome was documented on the basis of rigorous radiologic, electrophysiologic, and pulmonary function criteria. Theophylline, progesterone, and ritalin neither altered ventilatory response to CO2 nor permitted weaning from the ventilator. In contrast, peripheral chemoreceptor stimulants (intravenous doxapram; oral almitrine) effected an acute doubling of minute ventilation with appropriate decreases in PaCO2. However, a positive response to long-term therapy with almitrine could not be unequivocally shown. It was concluded that measurement of disrupted fibroblast PDHC following dichloroacetate activation constitutes an accurate assay for PDHC deficiency. PDHC deficiency must be considered in the differential diagnosis of the central hypoventilation syndrome; this appears to be the first report of such an association. Finally, a therapeutic trial of a peripheral chemoreceptor agonist is warranted in the management of central hypoventilation syndrome.
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PMID:Central hypoventilation syndrome in pyruvate dehydrogenase complex deficiency. 643 1

In 11 female patients with Fibromyalgia Syndrome (FS), biopsies from the m. vastus lateralis were analyzed, in order to reveal any possible changes which might explain muscular weakness and fatigue. Nineteen healthy subjects served as a control group. Light microscopy did not show any gross histopathological findings. Fiber composition and fiber areas did not differ between the two groups, except for a greater coefficient of variation of the area of type II A fibers and of the mean fiber area in the FS group. The number of capillaries per square millimeter and also the fiber area in relation to the capillaries, was lower in the FS patients. Analyses of enzymes showed decreased levels of 3-hydroxy-CoA-dehydrogenase and citrate synthase in the patient group. The reduced oxidative enzyme levels and capillarization indicate reduced physical activity, although this does not associate with muscle fiber hypotrophy.
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PMID:Muscle fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. 786 76

A patient with carnitine deficiency syndrome for tracheostomy and resection of tracheal granuloma was anesthetized with nitrous oxide and sevoflurane and vecuronium bromide. Potentiation of effect of vecuronium was minimal, and anesthetic course was uneventful. Carnitine is essential for transportation of long chain fatty acids into mitchondrial matrix. Its deficiency causes metabolic failure in skeletal muscle and accumulation of acyl-CoA in central nervous system. Carnitine deficiency syndrome is associated with a number of metabolic disorders of fatty acid. Signs and symptoms of the syndrome include skeletal muscle weakness, cardiomyopathy, liver disfunction, central nervous system disorders, hypoketotic hypoglycemia and so forth. Since fasting, infection, or shivering have been shown to deteriorate carnitine deficiency syndrome, there is a risk of triggering the acute episode perioperatively. Moreover, there is a possibility of prolonged effect of muscle relaxants and delay in emergence from anesthesia due to preexisting brain damage. These problems should be considered in perioperative period.
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PMID:[Anesthesia in a patient with carnitine deficiency syndrome]. 810 64

The acyl-CoA dehydrogenases (ACDs) are mitochondrial enzymes that dehydrogenate acyl-coenzyme A esters of different chain lengths. Inherited deficiencies of these dehydrogenases are commonly associated with muscle weakness and lipid storage. Numerous assays including spectrophotometric, fluorometric, chemical, and radiochemical procedures have been used, but there is need for a rapid, reproducible assay for the different acyl-CoA dehydrogenases in small frozen samples of human muscle biopsies. We describe a comparative study of dye-linked spectrophotometric assays of the long, medium, and short chain acyl-CoA dehydrogenases in frozen rat and human muscle samples. An optimal procedure is described confirming the value of glass-glass homogenization and assay of a 600g supernatant. Higher activities for all acyl-CoA dehydrogenases, citrate synthase, and cytochrome c oxidase were obtained in rat in contrast to human. The substrate-linked dye reduction method was found superior to the ferricenium or electron transfer flavoprotein acceptor systems. Application of the phenazine ethosulfate-DCPIP-linked method to medium-chain acyl-CoA dehydrogenase (MCAD) was studied in detail and the effect of immunoprecipitation of MCAD allowed for the determination of substrate specificity and the degree of crossover between long-, medium-, and short-chain ACD activity following immunoprecipitation. Finally, a comparison of the specificity and validity of the assay in a patient with MCAD deficiency was performed.
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PMID:Assay of acyl-CoA dehydrogenase activity in frozen muscle biopsies: application to medium-chain acyl-CoA dehydrogenase deficiency. 834 79


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