1/126. exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene.We report the first molecular defect in an NADH-dehydrogenase gene presenting as isolated myopathy. The proband had lifelong exercise intolerance but no weakness. A muscle biopsy showed cytochrome c oxidase (COX)-positive ragged-red fibers (RRFs), and analysis of the mitochondrial enzymes revealed complex I deficiency. sequence analysis of the mitochondrial genes encoding the seven NADH-dehydrogenase subunits showed a G-to-A transition at nucleotide 11832 in the subunit 4 (ND4) gene, which changed an encoded tryptophan to a stop codon. The mutation was heteroplasmic (54%) in muscle dna. Defects in mitochondrially encoded complex I subunits should be added to the differential diagnosis of mitochondrial myopathies.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
2/126. Myopathy with trabecular muscle fibers.A systematic review of muscle biopsies over a 15 year period in a large neurological hospital revealed 21 cases (7% of the total of non-inflammatory myopathies) with a distinctive pattern of myopathology and a limb-girdle clinical phenotype. The muscle pathology was dominated by a large prevalence (20-90%) of trabecular or lobulated fibers in which maldistribution of intermyofibrillar mitochondria produced a lobulated pattern of oxidative enzyme activity on transverse sections. The clinical picture was characterized by adult onset, slowly progressive muscle weakness affecting mainly proximal limb musculature, although mild distal weakness was also present in 60% of the cases. The trabecular pattern of oxidative enzyme reaction reflects maldistribution of the intermyofibrillar mitochondria; this may be caused by malfunction of a putative anchoring mechanism. While trabecular fibers can occur as a nonspecific alteration of muscle fibers in many diverse myopathies, the high prevalence of trabecular fibers as the dominant pathology in trabecular fiber myopathy makes it a distinctive (though not necessarily etiologically homogeneous) clinico-pathological entity.- - - - - - - - - - ranking = 2keywords = myopathies (Clic here for more details about this article) |
3/126. Mitochondrial 3243 A-->G mutation (MELAS mutation) associated with painful muscle stiffness.The mitochondrial mutation A-->G at nucleotide position 3243 is associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and other mitochondrial encephalomyopathies. We found this mutation in a 61-year-old patient who developed at the age of 54 a myopathy with painful muscle stiffness as the predominant symptom. Additionally hypacusis, a mild hemisensory syndrome and impaired glucose tolerance were present. Muscle histopathology showed few ragged red fibers. The mutation was detected heteroplasmatically in dna from muscle and blood. So far painful muscle stiffness has not been a known phenotype of the 3243 mutation.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
4/126. Familial skeletal myopathy with atrioventricular block.OBJECTIVE: We studied familial cases of skeletal myopathy with atrial fibrillation (Af) and atrioventricular (AV) block to compare the clinical features to other myopathies associated with cardiac abnormalities. methods: Neurologic, cardiologic, electrophysiologic, muscle pathology, and genetic studies were performed on the patients showing muscle weakness. patients: Four patients (a 63-year-old mother, 30 and 32-year-old sisters, and their maternal grandmother) and three healthy family members from three generations were studied. The mode of inheritance was suspected as autosomal dominant. RESULTS: Two sisters with congenital myopathy without rigid spine developed Af and AV block at the age of 28 and 18, respectively. The mother showed AV block, and underwent pacemaker implantation at the age of 63. The maternal grandmother had dilated cardiomyopathy, Af and severe lordosis. She died of stroke attacks and congestive heart failure at the age of 78. Muscle biopsy obtained from the mother and sisters showed myopathic changes without characteristic abnormalities. No mitochondrial dna mutations were found. Other inherited myopathies with cardiac complications were not suspected in this family. CONCLUSION: This Japanese family appears to belong to a new genetically heterogeneous group of autosomal dominant skeletal myopathy with severe AV block and Af.- - - - - - - - - - ranking = 2keywords = myopathies (Clic here for more details about this article) |
5/126. riboflavin therapy. Biochemical heterogeneity in two adult lipid storage myopathies.Two unrelated adult males, aged 36 (patient 1) and 25 (patient 2) years, presented with subacute carnitine-deficient lipid storage myopathy that was totally and partly responsive to riboflavin supplementation in the two patients, respectively. plasma acyl-carnitine and urinary organic acid profiles indicated multiple acyl coenzyme a dehydrogenase deficiency, which was mild in patient 1 and severe in patient 2. The activities of short-chain and medium-chain acyl coenzyme A dehydrogenases in mitochondrial fractions were decreased, especially in patient 2. This was in agreement with Western blotting results. Flavin-dependent complexes I and II were studied by immunoblotting and densitometric quantification of two-dimensional electrophoresis with comparable results. Complex I was present in normal amounts in both patients, whereas complex II was decreased only in the pretherapy muscle of patient 2. Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) concentrations in muscle and isolated mitochondria, and the activity of mitochondrial FAD pyrophosphatase, showed that patient 1 had low levels of FAD (46%) and FMN (49%) in mitochondria, with a significant increase (P < 0.01) in mitochondrial FAD pyrophosphatase (273%) compared with controls. Patient 2 had similar low levels of FAD and FMN in both total muscle (FAD and FMN 22% of controls) and mitochondria (FAD 26%; FMN 16%) and normal activity of mitochondrial FAD pyrophosphatase. All of these biochemical parameters were either totally or partly corrected after riboflavin therapy.- - - - - - - - - - ranking = 4keywords = myopathies (Clic here for more details about this article) |
6/126. Hereditary motor and sensory neuropathy type II (HMSN-II) and neurogenic muscle hypertrophy: a case report and literature review.We present two siblings affected by hereditary motor and sensory type II neuropathy (HMSN-II) with neuromyotonia, and associated with muscle hypertrophy of the thighs and calves in one. We review the literature about the association between HMSN-II, neuromyotonia and muscle hypertrophy. Muscle enlargement in HMSN-II is rare and may be sporadic or under genetic control. In our patient, muscle hypertrophy was sporadic and probably due to neuromyotonia. The relationship between muscle hypertrophy and neuromyotonia can be deduced by the fact that both conditions were reduced after diphenylhydantoin treatment (200 mg/day).- - - - - - - - - - ranking = 0.093149153559135keywords = myotonia (Clic here for more details about this article) |
7/126. A novel de novo mutation in the desmin gene causes desmin myopathy with toxic aggregates.OBJECTIVE: To determine the cause and pathogenic mechanisms of a 21-year-old patient's cardioskeletal myopathy. The patient's muscle atrophy and weakness began in distal parts of limbs; cardiac and facial muscles were later involved. BACKGROUND: desmin myopathy is a skeletal myopathy often associated with cardiomyopathy, caused by mutations in the desmin gene and characterized by desmin accumulation in affected muscle fibers, a leading marker of myofibrillar myopathies. Two kinds of deletions and seven missense mutations in the desmin gene have been identified. methods: Clinical examination, electron microscopy of muscle tissue, two-dimensional gel electrophoresis, dna sequencing, restriction enzyme analysis, and gene transfection were performed. RESULTS: Electron microscopy showed disruption of sarcomeres at Z discs and electron-dense aggregates in biopsied skeletal and heart muscle. Two-dimensional gel electrophoresis of the patient's skeletal muscle proteins showed massive accumulation of desmin. The authors identified a novel desmin mutation, L385P in one allele in the carboxyl end of the rod domain 2B in the patient's leukocytes and skeletal muscle; neither parent had the mutation. Serologic study and dna markers confirmed the de novo mutation. A peptide harboring desmin rod domains 2A and 2B with L385P tagged with green fluorescent protein induced cytoplasmic aggregates, nuclear dna condensation, and cell death. CONCLUSIONS: A novel de novo mutation, L385P, causes desmin myopathy. An expression study indicated the toxic effect of the L385P mutation.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
8/126. Rippling muscle disease: evidence for phenotypic and genetic heterogeneity.We describe the clinical features of a family with rippling muscle disease. Muscle stiffness and myalgia were the most prominent symptoms. Muscle rippling, although distinctive, was present in only 6 of the 11 affected family members, whereas persistent muscle contraction to muscle percussion was present in all affected adults. Although this persistent contraction resembled percussion myotonia, it was electrically silent and is therefore more aptly called "percussion contracture." We also observed two clinical features not emphasized in previously reported kindreds: mild but asymptomatic weakness of face or proximal muscles was present in 5 of 11 affected members, and 5 individuals also complained of toe walking after a prolonged period of inactivity, reflecting the disproportionate involvement of the calf muscles. The pedigree suggested autosomal dominant inheritance. Our linkage analysis excluded the region on chromosome 1q identified in a previous linkage study.- - - - - - - - - - ranking = 0.023287288389784keywords = myotonia (Clic here for more details about this article) |
9/126. X-linked myopathy with excessive autophagy: a clinicopathological study of five new families.In 1988, Kalimo et al. (Ann Neurol 23 (1988) 258)described a new type of X-linked myopathy in a Finnish family. The clinical course was characterized by slow progression of muscle weakness without loss of ambulation in childhood and no evidence of cardiac, respiratory, or central nervous system involvement. Muscle fibers were not necrotic and showed excessive autophagic activity and exocytosis of the phagocytosed material. These authors proposed the name X-linked myopathy with excessive autophagy. Subsequently, only one French family has been reported with similar clinical and histopathological data. We report here five new families with a total of eight affected boys with the same clinical and histopathological features as reported in the original families. Histopathological findings of an asymptomatic mother are also reported. Vacuolar changes in muscle fibers result both from invaginations of the sarcolemma along with a variable component of basal lamina and from an autophagic process. The complement c5b-9 membrane attack complex associated with MHC class 1 antigen and calcium deposits is involved in muscle fiber damage. Among the X-linked myopathies, the identification of this new type is of great interest because of its favorable prognosis and unique morphological findings.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
10/126. Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis.A severe muscle enolase deficiency, with 5% of residual activity, was detected in a 47-year-old man affected with exercise intolerance and myalgias. No rise of serum lactate was observed with the ischemic forearm exercise. Ultrastructural analysis showed focal sarcoplasmic accumulation of glycogen beta particles. The enzyme enolase catalyzes the interconversion of 2-phosphoglycerate and phosphoenolpyruvate. In adult human muscle, over 90% of enolase activity is accounted for by the beta-enolase subunit, the protein product of the ENO3 gene. The beta-enolase protein was dramatically reduced in the muscle of our patient, by both immunohistochemistry and immunoblotting, while alpha-enolase was normally represented. The ENO3 gene of our patient carries two heterozygous missense mutations affecting highly conserved amino acid residues; a G467A transition changing a glycine residue at position 156 to aspartate, in close proximity to the catalytic site, and a G1121A transition changing a glycine to glutamate at position 374. These mutations were probably inherited as autosomal recessive traits since the mother was heterozygous for the G467A and a sister was heterozygous for the G1121A transition. Our data suggest that ENO3 mutations result in decreased stability of mutant beta-enolase. Muscle beta-enolase deficiency should be considered in the differential diagnosis of metabolic myopathies due to inherited defects of distal glycolysis.- - - - - - - - - - ranking = 1keywords = myopathies (Clic here for more details about this article) |
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