1/182. Rapid progression of cardiomyopathy in mitochondrial diabetes.Cardiac involvement and its clinical course in a diabetic patient with a mitochondrial tRNA(Leu)(UUR) mutation at position 3243 is reported in a 54-year-old man with no history of hypertension. At age 46, an electrocardiogram showed just T wave abnormalities. At age 49, it fulfilled SV1 RV5 or 6>35 mm with strain pattern. At age 52, echocardiography revealed definite left ventricular (LV) hypertrophy, and abnormally increased mitochondria were shown in biopsied endomyocardial specimens. He was diagnosed as having developed hypertrophic cardiomyopathy associated with the mutation. However, at age 54, SV1 and RV5,6 voltages were decreased, and echocardiography showed diffuse decreased LV wall motion and LV dilatation. Because he had mitochondrial diabetes, the patient's heart rapidly developed hypertrophic cardiomyopathy, and then it seemed to be changing to a dilated LV with systolic dysfunction. Rapid progression of cardiomyopathy can occur in mitochondrial diabetes.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
2/182. Diagnostic utility of metabolic exercise testing in a patient with cardiovascular disease.Disproportionate exercise limitation in patients with cardiovascular disease is a common problem faced by clinical cardiologists and other physicians. Symptoms may be attributed to psychological factors or hypothetical pathophysiological mechanisms that are difficult to confirm clinically. This case report describes how the use of metabolic exercise testing in a 28 year old woman with morphologically and haemodynamically mild hypertrophic cardiomyopathy and severe exercise limitation led to the diagnosis of an alternative cause for the patient's symptoms, namely a primary disturbance of the mitochondrial respiratory chain probably caused by a nuclear encoded gene defect.- - - - - - - - - - ranking = 0.14285714285714keywords = myopathy (Clic here for more details about this article) |
3/182. adult onset limb-girdle type mitochondrial myopathy with a mitochondrial dna np8291 A-to-G substitution.We analyzed mitochondrial dna (mtDNA) from 7 patients in four families with adult onset limb-girdle type mitochondrial myopathy to clarify their genetic background. The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers. Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients. Southern blotting and direct sequence analyses showed an A-to-G homoplasmic transition at np8291 and intergenic COII/tRNA (Lys) 9bp deletion in all patients. This substitution was detected in only 2 of 600 control individuals including healthy subjects and patients with other neuromuscular disorders; these 2 individuals had diabetes mellitus and myotonic dystrophy, respectively. Consequently, the mtDNA transition at np8291 was a rare polymorphism. However, the 7 patients we studied had identical clinical, pathological, biochemical, and genetic features. Therefore, limb-girdle type mitochondrial myopathy with this rare polymorphism may form a subgroup of adult onset mitochondrial myopathy.- - - - - - - - - - ranking = 1.143102706621keywords = myopathy, dystrophy (Clic here for more details about this article) |
4/182. Nemaline myopathy and cardiomyopathy.A case report is presented in which a 4-year-old male is diagnosed with hypertrophic cardiomyopathy, respiratory distress, muscle hypotonia, and psychomotor retardation. Electron microscopic study of skeletal muscle biopsy revealed pathologic changes typical of congenital nemaline myopathy, and biochemical analysis revealed a disorder of mitochondrial fatty acid oxidation. Therefore a previously undescribed combination of a structural and metabolic myopathy is reported.- - - - - - - - - - ranking = 1.5714285714286keywords = myopathy (Clic here for more details about this article) |
5/182. Gene shifting: a novel therapy for mitochondrial myopathy.Mutations in mitochondrial dna (mtDNA) are the most frequent causes of mitochondrial myopathy in adults. In the majority of cases mutant and wild-type mtDNAs coexist, a condition referred to as mtDNA heteroplasmy; however, the relative frequency of each species varies widely in different cells and tissues. Nearly complete segregation of mutant and wild-type mtDNAs has been observed in the skeletal muscle of many patients. In such patients mutant mtDNAs pre-dominate in mature myofibers but are rare or undetectable in skeletal muscle satellite cells cultured in vitro. This pattern is thought to result from positive selection for the mutant mtDNA in post-mitotic myofibers and loss of the mutant by genetic drift in satellite cells. Satellite cells are dormant myoblasts that can be stimulated to re-enter the cell cycle and fuse with existing myofibers in response to signals for muscle growth or repair. We tested whether we could normalize the mtDNA genotype in mature myofibers in a patient with mitochondrial myopathy by enhancing the incorporation of satellite cells through regeneration following injury or muscle hypertrophy, induced by either eccentric or concentric resistance exercise training. We show a remarkable increase in the ratio of wild-type to mutant mtDNAs, in the proportion of muscle fibers with normal respiratory chain activity and in muscle fiber cross-sectional area after a short period of concentric exercise training. These data show that it is possible to reverse the molecular events that led to expression of metabolic myopathy and demonstrate the effectiveness of this form of 'gene shifting' therapy.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
6/182. Early onset of diabetes mellitus associated with the mitochondrial dna T14709C point mutation: patient report and literature review.We report a family in which a mother and son were affected with diabetes mellitus and myopathy characterized by ragged red fibers and suggestive of mitochondrial disease. Mitochondrial dna (mtDNA) analysis of dna isolated from peripheral blood showed a T-->C point mutation at nucleotide position 14709, in the transfer rna gene for glutamic acid. We review the association of diabetes and mtDNA mutations. This child's case is unusual because of the early onset of diabetes, which is more typical of mtDNA deletions.- - - - - - - - - - ranking = 0.14285714285714keywords = myopathy (Clic here for more details about this article) |
7/182. A new mitochondrial dna mutation (A3288G) in the tRNA(Leu(UUR)) gene associated with familial myopathy.We describe a family with a maternally inherited mitochondrial myopathy and an A3288G mutation in the tRNA(Leu(UUR)) gene. The proband had muscle cramping and mild weakness while her brother had long-standing limb and respiratory muscle weakness and her daughter had elevated serum CK. The mutation, which was nearly homoplasmic in muscle and heteroplasmic in blood, affects the TpsiC loop at a conserved site and was not found in 107 controls. This report confirms the frequent association of tRNA(Leu(UUR)) mutations with respiratory muscle involvement and bolsters the concept that tRNA(Leu(UUR)) is a hotspot for mtDNA mutations.- - - - - - - - - - ranking = 0.71428571428571keywords = myopathy (Clic here for more details about this article) |
8/182. Combination of mtDNA mutations in a patient with a mitochondrial multisystem syndrome.We report a patient who manifested a heterogeneous clinical presentation, including hypertrophic cardiomyopathy and hypothyroidism, with initially limited central nervous system involvement, and who harbored the mitochondrial (mt)dna A3243G mutation. MtDNA analysis also revealed deleted genomes in muscle and blood. This atypical molecular combination may have influenced the clinical phenotype.- - - - - - - - - - ranking = 0.14285714285714keywords = myopathy (Clic here for more details about this article) |
9/182. Clinical and molecular heterogeneity in very-long-chain acyl-coenzyme a dehydrogenase deficiency.Very-long-chain acyl-coenzyme a dehydrogenase (VLCAD) deficiency is an increasingly recognized defect of mitochondrial fatty acid beta-oxidation manifesting with episodes of metabolic decompensation or isolated recurrent myoglobinuria. In this report the clinical, biochemical, and molecular studies in a series of five patients (four Italian and one Spanish) with this disorder are discussed. Biochemical studies included the determination of fibroblast substrate oxidation rates and enzyme activity and Western blot analysis of VLCAD protein. Molecular analysis was performed by sequencing the VLCAD gene from the genomic dna. Clinical features were within the spectrum previously reported. Four patients presented in infancy or childhood with episodes of severe metabolic decompensation and dicarboxylic aciduria. Two exhibited cardiomyopathy. The fifth patient presented with isolated recurrent rhabdomyolysis, with no cardiomyopathy or dicarboxylic aciduria. In all patients a significant loss of VLCAD activity associated with a marked reduction of VLCAD protein levels occurred. Molecular analysis disclosed one novel missense mutation (Cys437Tyr) and four previously reported mutations, including two missense substitutions (Phe418Leu and Arg419Trp), a single amino acid deletion (Lys258del), and one splice site mutation (IVS8-C(-2)), which was present in all four Italian patients. All patients exhibited compound heterozygosity. The phenotypic variability and the high genotypic heterogeneity of this hereditary metabolic disorder is reported.- - - - - - - - - - ranking = 0.28571428571429keywords = myopathy (Clic here for more details about this article) |
10/182. Intragenic inversion of mtDNA: a new type of pathogenic mutation in a patient with mitochondrial myopathy.We report an unusual molecular defect in the mitochondrially encoded ND1 subunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitochondrial myopathy and isolated complex I deficiency. The mutation is an inversion of seven nucleotides within the ND1 gene, which maintains the reading frame. The inversion, which alters three highly conserved amino acids in the polypeptide, was heteroplasmic in the patient's muscle but was not detectable in blood. This is the first report of a pathogenic inversion mutation in human mtDNA.- - - - - - - - - - ranking = 0.71428571428571keywords = myopathy (Clic here for more details about this article) |
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