glycogen and Muscular-Diseases

PHKA1 mutations are causative for glycogen storage disease type IXd (GSDIXd), a myopathy that can be asymptomatic or associated with exercise intolerance, and rarely is accompanied by weakness or atrophy of limbs. Here we report a patient with GSDIXd who developed distal myopathy which was not accompanied by exercise intolerance at age 71. Muscle MRI revealed severe but gradual involvement of muscles with disease progression in the order of medial gastrocnemius, soleus, lateral gastrocnemius, and gluteus muscles. Muscle pathology revealed vacuolar changes with glycogen accumulation, and muscle enzymatic activity of phosphorylase b kinase was markedly decreased to 1.5 nmol of substrate utilized/min/mg protein (normal range: 39.5 ± 10.8). Collectively, the present findings suggest that PHKA1-associated distal myopathy is an adult-onset distal calf dominant myopathy which does not always present with exercise intolerance.

Topics: Adult; Aged; Distal Myopathies; Genetic Diseases, X-Linked; Glycogen; Glycogen Storage Disease; Humans; Japan; Male; Muscle, Skeletal; Muscular Diseases; Phosphorylase Kinase

The prevalence of cardiometabolic disease has reached an exponential rate of rise over the last decades owing to high fat/high caloric diet intake and satiety life style. Although the presence of dyslipidemia, insulin resistance, hypertension and obesity mainly contributes to the increased incidence of cardiometabolic diseases, population-based, clinical and genetic studies have revealed a rather important role for inherited myopathies and endocrine disorders in the ever-rising metabolic anomalies. Inherited metabolic and endocrine diseases such as glycogen storage and lysosomal disorders have greatly contributed to the overall prevalence of cardiometabolic diseases. Recent evidence has demonstrated an essential role for proteotoxicity due to autophagy failure and/or dysregulation in the onset of inherited metabolic and endocrine disorders. Given the key role for autophagy in the degradation and removal of long-lived or injured proteins and organelles for the maintenance of cellular and organismal homeostasis, this mini-review will discuss the potential contribution of autophagy dysregulation in the pathogenesis of inherited myopathies and endocrine disorders, which greatly contribute to an overall rise in prevalence of cardiometabolic disorders. Molecular, clinical, and epidemiological aspects will be covered as well as the potential link between autophagy and metabolic anomalies thus target therapy may be engaged for these comorbidities.

Topics: Autophagy; Cardiovascular Diseases; Endocrine System Diseases; Glycogen; Homeostasis; Humans; Insulin Resistance; Lysosomes; Metabolic Syndrome; Metabolism, Inborn Errors; Muscular Diseases; Obesity

Most of the glycogen metabolism disorders that affect skeletal muscle involve enzymes in glycogenolysis (myophosphorylase (PYGM), glycogen debranching enzyme (AGL), phosphorylase b kinase (PHKB)) and glycolysis (phosphofructokinase (PFK), phosphoglycerate mutase (PGAM2), aldolase A (ALDOA), β-enolase (ENO3)); however, 3 involve glycogen synthesis (glycogenin-1 (GYG1), glycogen synthase (GSE), and branching enzyme (GBE1)). Many present with exercise-induced cramps and rhabdomyolysis with higher-intensity exercise (i.e., PYGM, PFK, PGAM2), yet others present with muscle atrophy and weakness (GYG1, AGL, GBE1). A failure of serum lactate to rise with exercise with an exaggerated ammonia response is a common, but not invariant, finding. The serum creatine kinase (CK) is often elevated in the myopathic forms and in PYGM deficiency, but can be normal and increase only with rhabdomyolysis (PGAM2, PFK, ENO3). Therapy for glycogen storage diseases that result in exercise-induced symptoms includes lifestyle adaptation and carefully titrated exercise. Immediate pre-exercise carbohydrate improves symptoms in the glycogenolytic defects (i.e., PYGM), but can exacerbate symptoms in glycolytic defects (i.e., PFK). Creatine monohydrate in low dose may provide a mild benefit in PYGM mutations.

Topics: Animals; Glycogen; Humans; Metabolic Diseases; Muscular Diseases

Team sport athletes face a variety of nutritional challenges related to recovery during the competitive season. The purpose of this article is to review nutrition strategies related to muscle regeneration, glycogen restoration, fatigue, physical and immune health, and preparation for subsequent training bouts and competitions. Given the limited opportunities to recover between training bouts and games throughout the competitive season, athletes must be deliberate in their recovery strategy. Foundational components of recovery related to protein, carbohydrates, and fluid have been extensively reviewed and accepted. Micronutrients and supplements that may be efficacious for promoting recovery include vitamin D, omega-3 polyunsaturated fatty acids, creatine, collagen/vitamin C, and antioxidants. Curcumin and bromelain may also provide a recovery benefit during the competitive season but future research is warranted prior to incorporating supplemental dosages into the athlete's diet. Air travel poses nutritional challenges related to nutrient timing and quality. Incorporating strategies to consume efficacious micronutrients and ingredients is necessary to support athlete recovery in season.

Topics: Athletes; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Dietary Supplements; Energy Metabolism; Glycogen; Humans; Muscle Fatigue; Muscle, Skeletal; Muscular Diseases; Nutritional Physiological Phenomena; Nutritional Requirements; Seasons; Sports

The field of muscle glycogenoses has progressed in recent years by the identification of new disorders, and by reaching a better understanding of pathophysiology of the disorders and the physiology of glycogen metabolism.. In this review, we describe the clinical and pathological features of the three most recently described muscle glycogenoses caused by recessive mutations in GYG1, RBCK1 and PGM1. The three involved enzymes play different roles in glycogen metabolism. Glycogenin-1 (GYG1) is involved in the initial steps of glycogen synthesis, whereas phosphoglucomutase catalyzes two metabolic pathways; the connection between galactose and glycogen on one side, and glucose metabolism on the other side. The metabolic consequences of mutations in the ubiquitin ligase gene RBCK1 are still poorly understood. GYG1 deficiency has been associated with cardiomyopathies with abnormal storage material in the heart, but most cases present with a polyglucosan body myopathy without cardiac involvement.. The recent identification of new glycogenosis not only allows to improve the knowledge of glycogen metabolism, but also builds bridges with protein glycosylation and immune system.

Topics: Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycoproteins; Humans; Muscular Diseases; Mutation; Phosphoglucomutase; Transcription Factors; Ubiquitin-Protein Ligases

One large group of hereditary myopathies characterized by recurrent myoglobinuria, almost invariably triggered by exercise, comprises metabolic disorders of two main fuels, glycogen and long-chain fatty acids, or mitochondrial diseases of the respiratory chain. Differential diagnosis is required to distinguish the three conditions, although all cause a crisis of muscle energy. Muscle biopsy may be useful when performed well after the episode of rhabdomyolysis. Molecular genetics is increasingly the diagnostic test of choice to discover the underlying genetic basis.

Topics: Adenosine Triphosphate; Glycogen; Humans; Mitochondria; Muscular Diseases; Myoglobinuria; Renal Dialysis

Disorders of glycogen metabolism are inborn errors of energy homeostasis affecting primarily skeletal muscle, heart, liver, and, less frequently, the central nervous system. These rare diseases are quite variable in age of onset, symptoms, morbidity, and mortality. This review provides an update on disorders of glycogen metabolism affecting skeletal muscle exclusively or predominantly. From a pathogenetic perspective, we classify these diseases as primary, if the defective enzyme is directly involved in glycogen/glucose metabolism, or secondary, if the genetic mutation affects proteins which indirectly regulate glycogen or glucose processing. In addition to summarizing the most recent clinical reports in this field, we briefly describe animal models of human glycogen disorders. These experimental models are greatly improving the understanding of the pathogenetic mechanisms underlying the muscle degenerative process associated to these diseases and provide in vivo platforms to test new therapeutic strategies.

Topics: Animals; Disease Models, Animal; Glycogen; Glycogen Storage Disease; Humans; Lysosomal Storage Diseases; Muscular Diseases; Neuromuscular Diseases

Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). Fig. 1 Clinical algorithm for patients with exercise intolerance in whom a metabolic myopathy is suspected. CK-creatine kinase; COX-cytochrome c oxidase; CPT-carnitine palmitoyl transferase; cyt b-cytochrome b; mtDNA-mitochondrial DNA; nDNA-nuclear DNA; PFK-phosphofructokinase; PGAM-phosphoglycerate mutase; PGK-phosphoglycerate kinase; PPL-myophosphorylase; RRF-ragged red fibers; TFP-trifunctional protein deficiency; VLCAD-very long-chain acyl-coenzyme A dehydrogenase.

Topics: Algorithms; Glycogen; Humans; Lipid Metabolism Disorders; Metabolic Networks and Pathways; Metabolism, Inborn Errors; Mitochondrial Diseases; Models, Biological; Muscular Diseases

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are a common and effective treatment for hypercholesterolemia, with a low overall rate of side-effects. The most common complication is some degree of skeletal muscle myopathy, ranging from painless serum creatine kinase elevations to rhabdomyolysis. Unfortunately, the likelihood and/or severity of complications increases with the combination of statin treatment and physical activity. The specific pathways that mediate statin-associated myopathy are unclear, and research directly addressing the exacerbation with exercise is limited. Potential mechanisms include the induction of skeletal muscle fiber apoptosis, alterations in ubiquitin-proteasome pathway activity, mitochondrial dysfunction, and terpenoid depletion. In this review we provide an overview of research that specifically addresses the combination of statin-associated myopathy and physical activity and highlight some deficiencies in the available literature, as well as future directions for this important subset of statin-associated myopathy.

Topics: Creatine Kinase; Exercise; Glycogen; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Muscle, Skeletal; Muscular Diseases; Physical Education and Training; Risk Assessment; Risk Factors

There are 11 hereditary disorders of glycogen metabolism affecting muscle alone or together with other tissues, and they cause two main clinical syndromes: episodic, recurrent exercise intolerance with cramps, myalgia, and myoglobinuria; or fixed, often progressive weakness. Great strides have been made in our understanding of the molecular bases of these disorders, all of which show remarkable genetic heterogeneity. In contrast, the pathophysiological mechanisms underlying acute muscle breakdown and chronic weakness remain unclear. Although glycogen storage diseases have been studied for decades, new biochemical defects are still being discovered, especially in the glycolytic pathway. In addition, the pathogenesis of polyglucosan deposition is being clarified both in traditional glycogenoses and in disorders such as Lafora's disease. In some conditions, combined dietary and exercise regimens may be of help, and gene therapy, including recombinant enzyme replacement, is being actively pursued.

Topics: Diagnosis, Differential; Enzymes; Exercise Tolerance; Glycogen; Glycogen Storage Disease; Humans; Lafora Disease; Muscles; Muscular Diseases

Topics: Adenosine Triphosphate; Cell Membrane; Cytoskeletal Proteins; Desmin; Dystrophin; Glycogen; Humans; Intermediate Filament Proteins; Muscle Contraction; Muscles; Muscular Diseases; Mutation; Phosphofructokinases; Phosphorylase Kinase

Topics: Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Muscular Diseases

The glycogen storage myopathies are caused by enzyme defects in the glycogenolytic or in the glycolytic pathway affecting skeletal muscle alone or in conjunction with other tissues. The authors review recent findings in this area, including a new entity, aldolase deficiency, and the wealth of molecular genetic data that are rapidly accumulating. Despite this progress, genotype-phenotyp3 correlations are still murky in most glycogen storage myopathies.

Topics: Biopsy; Diagnosis, Differential; Fructose-Bisphosphate Aldolase; Genotype; Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Microscopy, Electron; Muscle, Skeletal; Muscular Diseases; Phenotype

The primary presentations of neuromuscular disease in the newborn period are hypotonia and weakness. Although metabolic myopathies are inherited disorders that present from birth and may present with subtle to marked neonatal hypotonia, a number of these defects are diagnosed classically in childhood, adolescence, or adulthood. Disorders of glycogen, lipid, or mitochondrial metabolism may cause three main clinical syndromes in muscle, namely, (1) progressive weakness with hypotonia (e.g., acid maltase, debrancher enzyme, and brancher enzyme deficiencies among the glycogenoses; carnitine uptake and carnitine acylcarnitine translocase defects among the fatty acid oxidation (FAO) defects; and cytochrome oxidase deficiency among the mitochondrial disorders) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or myoglobinuria (with or without cramps), e.g., phosphorylase, phosphofructokinase, and phosphoglycerate kinase among the glycogenoses and carnitine palmitoyltransferase II deficiency among the disorders of FAO or (3) both (e.g., long-chain or very long-chain acyl coenzyme A (CoA) dehydrogenase, short-chain L-3-hydroxyacyl-CoA dehydrogenase, and trifunctional protein deficiencies among the FAO defects). Episodes of exercise-induced myoglobinuria tend to present in later childhood or adolescence; however, myoglobinuria in the first year of life may occur in FAO disorders during catabolic crises precipitated by fasting or infection. The following is a survey of genetic disorders of glycogen and lipid metabolism resulting in myopathy, focusing primarily on those defects, to date, that have presented in the neonatal or early infancy period. Disorders of mitochondrial metabolism are discussed in another chapter.

Topics: Fatty Acids; Glycogen; Glycolysis; Humans; Infant, Newborn; Metabolism, Inborn Errors; Mitochondrial Myopathies; Muscle, Skeletal; Muscular Diseases

The molecular heterogeneities of enzyme abnormality have been identified successfully since 1990 for major clinical entities of glycogenolytic and glycolytic defects in skeletal muscle. The interchange between clinical medicine and basic science, which enabled these achievements, has a long history. This review introduces several important examples of this interchange, which has borne much fruit in the comprehensive understanding of glycogenolysis-glycolysis in skeletal muscle and the related defects that cause various metabolic diseases. For instance, the presence of "glycogen synthase" was mainly suggested by the pathophysiology of McArdle's disease. Clinical manifestations of muscle phosphofructokinase (PFK) deficiency have indicated that there could be PFK isozymes under separate genetic control. Although glycolysis is a unidirectional pathway, enzyme defects at each step do not necessarily cause similar manifestations. Glycogen accumulation is mostly associated with enzyme defects in glycogenolysis and in the first stage of glycolysis. Since the original report of phosphoglycerate mutase deficiency in 1981, no newly recognized glycolytic defects have been presented. Glycolytic steps for which no enzyme deficiency has been identified seem to provide another important impetus for further study of "fail-safe" mechanisms in regard to monogenic disorders.

Topics: Biochemical Phenomena; Biochemistry; Clinical Medicine; Fructosediphosphates; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type V; Humans; Isoenzymes; Muscular Diseases; Phosphofructokinase-1; Phosphoglycerate Kinase

Phosphofructokinase (PFK) plays a major role in glycolysis. Deficiency of PFK-M is characterized by muscle weakness due to fuel crisis in exercising muscles. To elucidate the gene defect of PFK-deficient patients, we have cloned and determined the complete structure and transcription mechanism of human PFK-M mRNA and gene. Molecular defects were investigated in three unrelated Japanese family cases. The first case was characterized by a point mutation at the donor site of intron 15 of the PFK-M gene. Cryptic splicing resulted in a 25 amino acid truncation in the patient's PFK-M. The second case possessed a point mutation at the donor site of intron 19, resulting in the skipping of exon 19 and the truncation of 55 amino acids. In the third case, a missense mutation was identified in the coding region. The review of an updated mutation repertoire indicates the heterogeneity of the molecular mechanism of the disease.

Topics: Animals; Base Sequence; DNA Mutational Analysis; Female; Geobacillus stearothermophilus; Glycogen; Humans; Male; Molecular Sequence Data; Muscular Diseases; Phosphofructokinase-1; Rabbits; RNA, Messenger

Topics: Carbohydrate Metabolism; Enzymes; Glucose; Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Lactates; Lactic Acid; Muscles; Muscular Diseases

Topics: Animals; Glycogen; Humans; Lipid Metabolism; Mitochondria, Muscle; Muscles; Muscular Diseases

This review will briefly outline the major steps of glycogen metabolism in muscle and the role of glycogen as a source of energy in different types of exercise. There are nine specific enzyme defects of glycogen metabolism or glycolysis affecting muscle. Each of the nine glycogenoses will be discussed in terms of typical and variant clinical presentation, genetic transmission, muscle biopsy and biochemical findings. The proposed pathophysiology of the various symptoms and signs will be presented and the many unsolved problems in this area will be discussed.

Topics: Biopsy; Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Metabolic Diseases; Muscles; Muscular Diseases; Phosphofructokinase-1

Topics: alpha-Glucosidases; AMP Deaminase; Carnitine; Carnitine O-Palmitoyltransferase; Creatine Kinase; Female; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VII; Humans; Lipid Metabolism, Inborn Errors; Male; Metabolism, Inborn Errors; Muscular Diseases; Phosphofructokinase-1; Phosphorylase a

Topics: Carnitine; Carnitine O-Palmitoyltransferase; Glycogen; Glycogen Storage Disease; Humans; Mitochondria, Muscle; Muscular Diseases; Nucleotides

Topics: Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Humans; Liver Glycogen; Muscles; Muscular Diseases

Topics: Cardiomyopathies; Glucosephosphate Dehydrogenase Deficiency; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Hepatomegaly; Humans; Kidney Diseases; Liver Cirrhosis; Liver Diseases; Liver Glycogen; Muscular Diseases; Pectins; Polysaccharides; Splenomegaly

Topics: Fructose-Bisphosphate Aldolase; Glucosyltransferases; Glycogen; Glycolysis; Humans; Isoenzymes; L-Lactate Dehydrogenase; Muscle Contraction; Muscle Proteins; Muscles; Muscular Diseases; Phosphoric Monoester Hydrolases

Topics: Adenosine Triphosphatases; Adolescent; Adult; Alkaline Phosphatase; Animals; Cats; Child; Child, Preschool; Electron Transport Complex IV; Fructose-Bisphosphate Aldolase; Glucosyltransferases; Glycogen; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Middle Aged; Muscles; Muscular Diseases; Muscular Dystrophies; Myofibrils; Succinate Dehydrogenase

Topics: Adolescent; Biopsy; Child; Child, Preschool; Cytoplasm; Diet Therapy; Electromyography; Female; Glycogen; Humans; Infant; Lipid Metabolism; Male; Mitochondria, Muscle; Motor Neurons; Muscles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Necrosis; Nervous System Diseases; Obesity; Obesity Hypoventilation Syndrome

It is generally believed that a diet high in carbohydrate improves exercise tolerance in patients with carnitine palmitoyltransferase II (CPT II) deficiency, but it has never been systematically investigated. The authors investigated the effect of a high- vs low-carbohydrate diet on exercise tolerance in four patients with CPT II, who cycled at a constant workload of 50% of VO2max. Exercise tolerance, assessed by exercise duration and perceived exertion, improved on the carbohydrate-rich diet.

Topics: Alanine; Blood Glucose; Carnitine O-Palmitoyltransferase; Creatine Kinase; Creatine Kinase, MM Form; Dietary Carbohydrates; Dietary Fats; Exercise Test; Exercise Tolerance; Fatty Acids, Nonesterified; Glycerol; Glycogen; Heart Rate; Humans; Insulin; Isoenzymes; Lactates; Lipid Metabolism, Inborn Errors; Muscular Diseases; Norepinephrine

Since the time sequence of exercise-induced muscle soreness corresponds well with the time sequence of exercise-induced morphological changes in animal skeletal muscle, it has been suggested that muscle soreness is related to an inflammatory response. Prostaglandins are assumed to play a role in the inflammatory process. The influence of a cyclo-oxygenase-inhibiting drug (flurbiprofen) on the subjective symptoms of soreness and eventual structural changes was investigated in six male subjects. The subjects performed one concentric and two eccentric work bouts of 30 min at 80% of the individual maximal work load on the bicycle ergometer. Muscle biopsies taken before, immediately after, and 24 h after work were used to examine structural, ultrastructural changes as well as for assessment of glycogen content. Plasma levels of muscle enzymes and subjective soreness were determined at regular intervals. Eccentric work elicited muscle soreness in all subjects: however, the soreness was consistently less in the second eccentric trial. No significant enzyme release was noticed in any of the subjects, whereas ultrastructural changes were restricted to the mitochondria. No influence of flurbiprofen on subjective soreness was noticed. After both eccentric trials muscle glycogen was lower 24 h after work compared to the content immediately after work. The results suggest that eccentric exercise interferes with glycogen synthesis and that prostaglandins do not play a major role in exercise-induced muscle soreness.

Topics: Adult; Exercise Test; Flurbiprofen; Glycogen; Humans; Inflammation; Male; Muscle Contraction; Muscles; Muscular Diseases; Physical Exertion; Propionates

Both type 1 (PSSM1) and type 2 polysaccharide storage myopathy (PSSM2) are characterised by aggregates of abnormal polysaccharide in skeletal muscle. Whereas the genetic basis for PSSM1 is known (R309H GYS1), the cause of PSSM2 in Quarter Horses (PSSM2-QH) is unknown and glycogen concentrations not defined.. To characterise the histopathological and biochemical features of PSSM2-QH and determine if an associated monogenic variant exists in genes known to cause glycogenosis.. Retrospective case control.. Sixty-four PSSM2-QH, 30 PSSM1-QH and 185 control-QH were identified from a biopsy repository and clinical data, histopathology scores (0-3), glycogen concentrations and selected glycolytic enzyme activities compared. Coding sequences of 12 genes associated with muscle glycogenoses were identified from whole genome sequences and compared between seven PSSM2-QH and five control-QH.. Exertional rhabdomyolysis in PSSM2-QH occurred predominantly in barrel racing and working cow/roping performance types and improved with regular exercise and a low starch/fat-supplemented diet. Histopathological scores, including the amount of amylase-resistant polysaccharide (PSSM2-QH 1.4 ± 0.6, PSSM1-QH 2.1 ± 0.3, control-QH 0 ± 0, p < 0.001), and glycogen concentrations (PSSM2-QH 129 ± 62, PSSM1-QH 175 ± 9, control-QH 80 ± 27 mmol/kg, p < 0.0001) were intermediate in PSSM2-QH with significant differences among groups. In PSSM2-QH, abnormal polysaccharide had a less filamentous ultrastructure than PSSM1-QH and phosphorylase and phosphofructokinase activities were normal. Seventeen of 30 PSSM2-QH with available pedigrees descended from one of three stallions within four generations. Of the 29 predicted high or moderate impact genetic variants identified in candidate genes, none were present in only PSSM2-QH and absent in control-QH.. Analyses of PSSM2-QH and PSSM1-QH were performed on shipped samples, controls on frozen samples.. PSSM2-QH is a novel glycogen storage disorder that is not the result of a mutation in genes currently known to cause muscle glycogenoses in other species.. Ambos os tipos 1 e 2 de miopatia por acúmulo de polissacarídeo (PSSM) são caracterizados por agregados de polissacarídeos anormais no músculo esquelético. Enquanto a base genética do PSSM 1 é conhecida (R309H GYS1), a causa do PSSM2 em cavalos Quarto de Milha (PSSM2-QH) é desconhecida, e a concentração de glicogênio não é definida.. Identificar as características histopatológicas e bioquímicas do PSSM-QH e determinar se há uma variante monogênica em genes conhecidos por causar glicogenose.. Caso controlado retrospectivo.. 64 PSSM2-QH, 30 PSSM1-QH e 185 QH controles foram identificados em um arquivo de dados. Informação clínica, achados histológicos (escala 0-3), concentração de glicogênio e atividade enzimática de algumas enzimas glicolíticas foram comparadas. Sequências codificadas de 12 genes associados com glicogenose muscular foram identificados nas sequências genômicas completas, e comparadas entre 7 PSSM2-QH e 5 QH controles.. Rabdomiólise por exercício em PSSM2-QH ocorreu predominantemente em cavalos de corrida de tambor e cavalos de team roping/trabalho com gado, e melhorou com exercício regular e uma dieta com baixo amido e alta gordura. A escala histopatológica, incluindo a quantidade de polissacarídeos resistentes à amilase (PSSM2-QH 1.4 ± 0.6, PSSM1-QH 2.1 ± 0.3, controle-QH 0 ± 0, P < 0.001), e concentrações de glicogênio (PSSM2-QH 129 ± 62, PSSM1-QH 175 ± 9, controle-QH 80 ± 27 mmol/kg, P < 0.0001) foram intermediárias em PSSM2-QH com diferença significante entre grupos. Em PSSM2-QH, polissacarídeo anormal teve uma ultraestrutura menos filamentosa do que PSSM1-QH e as atividades de fosforilase e fosfofrutoquinase foram normais. Dezessete dos 30 PSSM2-QH com pedigree disponível descendiam de 1 de 3 garanhões dentro de 4 gerações. Das 29 variações genéticas preditas a terem impacto moderado ou alto como genes candidatos, nenhuma estava presente apenas em PSSM2-QH e ausente no grupo controle-QH. PRINCIPAIS LIMITAÇÕES: As análises feitas nas amostras de PSSM2-QH e PSSM1-QH foram realizadas em amostras enviadas por correio, e as amostras dos animais controles eram amostras congeladas. CONCLUSÕES: PSSM2-QH é uma nova doença por acúmulo de glicogênio que não é o resultado de uma mutação nos genes conhecidos por causarem glicogenose muscular em outras espécies.

Topics: Animals; Cattle; Cattle Diseases; Female; Glycogen; Glycogen Storage Disease; Horse Diseases; Horses; Male; Muscle, Skeletal; Muscular Diseases; Polysaccharides; Retrospective Studies; Rhabdomyolysis

Myopathies associated with monoclonal gammopathy are relatively uncommon and underrecognized, treatable myopathies, and include sporadic late onset nemaline myopathy, light chain amyloid myopathy, and a recently described vacuolar myopathy with monoclonal gammopathy and stiffness (VAMGS). Herein, we report a new subtype of monoclonal gammopathy-associated myopathy (MGAM) in a polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) patient.. Case report.. A 51-year-old woman presented with a 6-month history of progressive bilateral foot drop, lower limb edema, and a 15-lb weight loss. She denied muscle stiffness. Neurologic exam showed severe distal weakness, mild proximal weakness, and length-dependent sensory deficits. Laboratory studies revealed biclonal gammopathy (IgG kappa and IgA lambda), thrombocytosis, and elevated vascular endothelial growth factor. Creatine kinase was normal. Electrodiagnostic studies identified mixed demyelinating and axonal polyradiculoneuropathy and a superimposed proximal myopathy. Gluteus medius biopsy demonstrated scattered fibers with glycogen-filled vacuoles, similar to VAMGS, with additional rare myofibers containing polyglucosan bodies. She was diagnosed with POEMS syndrome and concomitant glycogen storage myopathy. Next-generation sequencing of glycogen storage and polyglucosan body myopathy-related genes was unrevealing. Proximal weakness resolved after autologous stem cell transplant.. This patient expands a spectrum of MGAM. Recognition of this condition and other subtypes of MGAM is of utmost important because they are treatable.

Topics: Female; Glycogen; Humans; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Muscular Diseases; Paraproteinemias; POEMS Syndrome; Vascular Endothelial Growth Factor A

Early onset myopathies are a clinically and histologically heterogeneous monogenic diseases linked to approximately 90 genes. Molecular diagnosis is challenging, especially in patients with a mild phenotype. We describe a 26-year-old man with neonatal hypotonia, motor delay and seizures during infancy, and non-progressive, mild muscular weakness in adulthood. Serum Creatine kinase level was normal. Whole-body muscle MRI showed thin muscles, and brain MRI was unremarkable. A deltoid muscle biopsy showed glycogen storage. WGS revealed a de novo 1.4 Mb-deletion of chromosome 14, confirmed by Array-CGH. This microdeletion causes the loss of ten genes including RALGAPA1, encoding for RalA, a regulator of glucose transporter 4 (GLUT4) expression at the membrane of myofibers. GLUT4 was overexpressed in patient's muscle. Here we highlight the importance to search for chromosomal alterations in the diagnostic workup of early onset myopathies.

Topics: Adult; Chromosomes, Human, Pair 14; Glycogen; GTPase-Activating Proteins; Humans; Infant, Newborn; Male; Muscle Hypotonia; Muscular Diseases; Nerve Tissue Proteins; Phenotype

Vitamin D deficiency leads to pathologies of multiple organ systems including skeletal muscle. Patients with severe vitamin D deficiency exhibit muscle weakness and are susceptible to frequent falls. Mice lacking a functional vitamin D receptor (VDR) develop severe skeletal muscle atrophy immediately after weaning. But the root cause of myopathies when vitamin D signalling is impaired is unknown. Because vitamin D deficiency leads to metabolic changes as well, we hypothesized that the skeletal muscle atrophy in mice lacking VDR may have a metabolic origin.. We analysed wild-type (WT) mice as well as vitamin D receptor null (vdr-/-) mice for skeletal muscle proteostasis, energy metabolism, systemic glucose homeostasis, and muscle glycogen levels. Dysregulation of signalling pathways as well as the glycogen synthesis and utilization machinery were also analysed using western blots. qRT-PCR assays were performed to understand changes in mRNA levels.. Skeletal muscles of vdr-/- exhibited higher expression levels of muscle-specific E3 ubiquitin ligases and showed increased protein ubiquitination, suggesting up-regulation of protein degradation. Foxo1 transcription factor was activated in vdr-/- while Foxo3 factor was unaffected. Fasting protein synthesis as well as mTORC1 pathways were severely down-regulated in vdr-/- mice. Skeletal muscle ATP levels were low in vdr-/- (0.58 ± 0.18 μmol/mL vs. 1.6 ± 0.0.14 μmol/mL, P = 0.006), leading to increased AMPK activity. Muscle energy deprivation was not caused by decreased mitochondrial activity as we found the respiratory complex II activity in vdr-/- muscles to be higher compared with WT (0.29 ± 0.007 mU/μL vs. 0.16 ± 0.005 mU/μL). vdr-/- mice had lower fasting blood glucose levels (95 ± 14.5 mg/dL vs. 148.6 ± 6.1 mg/dL, P = 0.0017) while they exhibited hyperlactataemia (7.42 ± 0.31 nmol/μL vs. 4.95 ± 0.44 nmol/μL, P = 0.0032), suggesting systemic energy deficiency in these mice. Insulin levels in these mice were significantly lower in response to intraperitoneal glucose injection (0.69 ± 0.08 pg/mL vs. 1.11 ± 0.09 pg/mL, P = 0.024). Skeletal muscles of these mice exhibit glycogen storage disorder characterized by increased glycogen accumulation. The glycogen storage disorder in vdr-/- muscles is driven by increased glycogen synthase activity and decreased glycogen phosphorylase activity. Increased glycogenin expression supports higher levels of glycogen synthesis in these muscles.. The results presented show that lack of vitamin D signalling leads to a glycogen storage defect in the skeletal muscles, which leads to muscle energy deprivation. The inability of vdr-/- skeletal muscles to use glycogen leads to systemic defects in glucose homeostasis, which in turn leads to proteostasis defects in skeletal muscles and atrophy.

Topics: Animals; Glycogen; Humans; Mice; Muscle, Skeletal; Muscular Diseases; Receptors, Calcitriol; Vitamin D Deficiency

Critical illness myopathy (CIM) is a debilitating condition characterized by the preferential loss of the motor protein myosin. CIM is a by-product of critical care, attributed to impaired recovery, long-term complications, and mortality. CIM pathophysiology is complex, heterogeneous and remains incompletely understood; however, loss of mechanical stimuli contributes to critical illness-associated muscle atrophy and weakness. Passive mechanical loading and electrical stimulation (ES) therapies augment muscle mass and function. While having beneficial outcomes, the mechanistic underpinning of these therapies is less known. Therefore, here we aimed to assess the mechanism by which chronic supramaximal ES ameliorates CIM in a unique experimental rat model of critical care.. Rats were subjected to 8 days of critical care conditions entailing deep sedation, controlled mechanical ventilation, and immobilization with and without direct soleus ES. Muscle size and function were assessed at the single cell level. RNAseq and western blotting were employed to understand the mechanisms driving ES muscle outcomes in CIM.. Following 8 days of controlled mechanical ventilation and immobilization, soleus muscle mass, myosin : actin ratio, and single muscle fibre maximum force normalized to cross-sectional area (CSA; specific force) were reduced by 40-50% (P < 0.0001). ES significantly reduced the loss of soleus muscle fibre CSA and myosin : actin ratio by approximately 30% (P < 0.05) yet failed to effect specific force. RNAseq pathway analysis revealed downregulation of insulin signalling in the soleus muscle following critical care, and GLUT4 trafficking was reduced by 55% leading to an 85% reduction of muscle glycogen content (P < 0.01). ES promoted phosphofructokinase and insulin signalling pathways to control levels (P < 0.05), consistent with the maintenance of GLUT4 translocation and glycogen levels. AMPK, but not AKT, signalling pathway was stimulated following ES, where the downstream target TBC1D4 increased 3 logFC (P = 0.029) and AMPK-specific P-TBC1D4 levels were increased approximately two-fold (P = 0.06). Reduction of muscle protein degradation rather than increased synthesis promoted soleus CSA, as ES reduced E3 ubiquitin proteins, Atrogin-1 (P = 0.006) and MuRF1 (P = 0.08) by approximately 50%, downstream of AMPK-FoxO3.. ES maintained GLUT4 translocation through increased AMPK-TBC1D4 signalling leading to improved muscle glucose homeostasis. Soleus CSA and myosin content was promoted through reduced protein degradation via AMPK-FoxO3 E3 ligases, Atrogin-1 and MuRF1. These results demonstrate chronic supramaximal ES reduces critical care associated muscle wasting, preserved glucose signalling, and reduced muscle protein degradation in CIM.

Topics: Actins; AMP-Activated Protein Kinases; Animals; Critical Illness; Electric Stimulation Therapy; Glucose; Glucose Transporter Type 4; Glycogen; Insulin; Muscle, Skeletal; Muscular Atrophy; Muscular Diseases; Myosins; Rats

Rheumatoid arthritis (RA) is accompanied by pain, inflammation and muscle weakness. Skeletal muscle inflammation and inactivity are independently associated with muscle insulin resistance and atrophy. Our objective was to identify early molecular and biochemical markers in muscle from a rodent model of RA relative to control and subsequently identify commonality in muscle gene expression between this model and muscle from RA patients. Pain behaviour and locomotor activity were measured in a collagen-induced arthritis (CIA) model of RA (n = 9) and control (n = 9) rats. Energy substrates and metabolites, total alkaline-soluble protein:DNA ratio and mRNA abundance of 46 targeted genes were also determined in Extensor digitorum longus muscle. Expression of targeted mRNAs was quantified in Vastus Lateralis muscle from RA patients (n = 7) and healthy age-matched control volunteers (n = 6). CIA rats exhibited pain behaviour (p<0.01) and reduced activity (p<0.05) compared to controls. Muscle glycogen content was less (p<0.05) and muscle lactate content greater (p<0.01) in CIA rats. The bioinformatics analysis of muscle mRNA abundance differences from the control, predicted the activation of muscle protein metabolism and inhibition of muscle carbohydrate and fatty acid metabolism in CIA rats. Compared to age-matched control volunteers, RA patients exhibited altered muscle mRNA expression of 8 of the transcripts included as targets in the CIA model of RA. In conclusion, muscle energy metabolism and metabolic gene expression were altered in the CIA model, which was partly corroborated by targeted muscle mRNA measurements in RA patients. This research highlights the negative impact of RA on skeletal muscle metabolic homeostasis.

Topics: Aged; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Biomarkers; Disease Models, Animal; Female; Glycogen; Humans; Inflammation; Locomotion; Middle Aged; Muscle, Skeletal; Muscular Diseases; Myalgia; Rats; Rats, Inbred Lew; RNA, Messenger; Transcriptome

Topics: Adolescent; Adult; Aged; Calcium Channels, L-Type; Cross-Sectional Studies; Female; Glycogen; Humans; Hypokalemic Periodic Paralysis; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Mutation; Vacuoles; Young Adult

Development of white striping (WS) and wooden breast (WB) in broiler breast meat have been linked to hypoxia, but their etiologies are not fully understood. This study aimed at investigating absolute expression of hypoxia-inducible factor-1 alpha subunit (HIF1A) and genes involved in stress responses and muscle repair using a droplet digital polymerase chain reaction. Total RNA was isolated from pectoralis major collected from male 6-week-old medium (carcass weight ≤ 2.5 kg) and heavy (carcass weight > 2.5 kg) broilers. Samples were classified as "non-defective" (n = 4), "medium-WS" (n = 6), "heavy-WS" (n = 7) and "heavy-WS+WB" (n = 3) based on abnormality scores. The HIF1A transcript was up-regulated in all of the abnormal groups. Transcript abundances of genes encoding 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4), lactate dehydrogenase-A (LDHA), and phosphorylase kinase beta subunit (PHKB) were increased in heavy-WS but decreased in heavy-WS+WB. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was up-regulated in non-defective samples. The muscle-specific mu-2 isoform of glutathione S-transferases (GSTM2) was up-regulated in the abnormal samples, particularly in the heavy groups. The genes encoding myogenic differentiation (MYOD1) and myosin light chain kinase (MYLK) exhibited similar expression pattern, of which medium-WS and heavy-WS significantly increased compared to non-defective whereas expression in heavy-WS+WB was not different from either non-defective or WS-affected group. The greatest and the lowest levels of calpain-3 (CAPN3) and delta-sarcoglycan (SCGD) were observed in heavy-WS and heavy-WS+WB, respectively. Based on micrographs, the abnormal muscles primarily comprised fibers with cross-sectional areas ranging from 2,000 to 3,000 μm2. Despite induced glycolysis at the transcriptional level, lower stored glycogen in the abnormal muscles corresponded with the reduced lactate and higher pH within their meats. The findings support hypoxia within the abnormal breasts, potentially associated with oversized muscle fibers. Between WS and WB, divergent glucose metabolism, cellular detoxification and myoregeneration at the transcriptional level could be anticipated.

Topics: Animals; Chickens; Gene Expression Regulation; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lactic Acid; Male; Muscle, Skeletal; Muscular Diseases; Pectoralis Muscles; Poultry Diseases; RNA, Messenger

This study was conducted to characterize metabolic differences between high feed efficiency (HFE) and low feed efficiency (LFE) chickens to investigate why feed efficient chickens are more susceptible to muscle abnormalities such as wooden breast disease. Gene expression profiles were generated by RNA sequencing of pectoralis major muscle samples from 10 HFE and 13 LFE broiler chickens selected from a modern broiler population. Metabolism-associated differentially expressed genes were identified and interpreted by Ingenuity Pathway Analysis and literature mining. Our RNA-seq data indicate decreased glycolytic capacity, increased fatty acid uptake, mitochondrial oxidation of fatty acids, and several other metabolic alterations in the pectoralis major muscle of HFE chickens. We also quantified glycogen content of the pectoralis major muscle and found that the HFE chickens had a significantly (P ≤ 0.05) lower glycogen content. Collectively, this study indicates extensive metabolic differences in the pectoralis major muscle between HFE and LFE chickens and helps identify metabolic features of susceptibility to muscle disorders in modern broiler chickens.

Topics: Animal Nutritional Physiological Phenomena; Animals; Chickens; Fatty Acids; Glycogen; Muscular Diseases; Pectoralis Muscles; Poultry Diseases; Sequence Analysis, RNA; Transcriptome

Type 1 polysaccharide storage myopathy (PSSM1) is a glycogen storage disorder of known cause whereas the basis for type 2 PSSM (PSSM2) is unknown. The same diet and exercise regime prescribed for PSSM1 is recommended for PSSM2; however, the benefit of these recommendations for PSSM2 is undocumented. The objectives of this study were to determine traits of PSSM2 Warmblood horses (WB), determine the changes in exercise responses that occur with a recommended low-starch/fat-supplemented diet and exercise regime, and determine if glycogen concentrations correspond to the severity of signs. Owners of PSSM2 WB (2008-2016), completed a retrospective questionnaire regarding their horse. Glycogen concentrations were analyzed in skeletal muscle of PSSM2 WB (n = 36) obtained prior to recommendations and in control WB with no evident myopathy (n = 23). Chi-square, Fisher's exact, McNemar's tests with Bonferroni correction and Mann Whitney testing were utilized. Abnormal exercise responses reported by owners, began at approximately 6 years of age and included a decline in performance, a reluctance to collect and reluctance to go forward in over 50% of horses. With the recommended diet and exercise regime, 80% of PSSM2 WB owners reported an overall improvement with significant decreases in the proportion of horses showing a decline in performance and rhabdomyolysis. However, 53% of PSSM2 WB were still not advancing as expected with reluctance to go forward and collect persisting in approximately one third of horses. Median muscle glycogen concentrations did not differ between PSSM2 WB and WB with no evident myopathy. PSSM2 WB with the highest glycogen concentrations were significantly more likely to show a decline in performance than those with lower glycogen concentrations. In conclusion, diet and exercise recommendations ideal for PSSM1 improve but do not eliminate the decline in performance and reluctance to go forward under saddle characteristic of PSSM2.

Topics: Animal Feed; Animals; Glycogen; Glycogen Storage Disease Type II; Horse Diseases; Horses; Muscle, Skeletal; Muscular Diseases; Physical Conditioning, Animal; Starch

We investigated metabolism and physiological responses to exercise in an 18-year-old woman with multiple congenital abnormalities and exertional muscle fatigue, tightness, and rhabdomyolysis.. We studied biochemistry in muscle and fibroblasts, performed mutation analysis, assessed physiological responses to forearm and cycle-ergometer exercise combined with stable-isotope techniques and indirect calorimetry, and evaluated the effect of IV glucose infusion and oral sucrose ingestion on the exercise response.. Phosphoglucomutase type 1 (PGM1) activity in muscle and fibroblasts was severely deficient and PGM1 in muscle was undetectable by Western blot. The patient was compound heterozygous for missense (R422W) and nonsense (Q530X) mutations in PGM1. Forearm exercise elicited no increase in lactate, but an exaggerated increase in ammonia, and provoked a forearm contracture. Comparable to patients with McArdle disease, the patient developed a 'second wind' with a spontaneous fall in exercise heart rate and perceived exertion. Like in McArdle disease, this was attributable to an increase in muscle oxidative capacity. Carbohydrate oxidation was blocked during exercise, and the patient had exaggerated oxidation of fat to fuel exercise. Exercise heart rate and perceived exertion were lower after IV glucose and oral sucrose. Muscle glycogen level was low normal.. The second wind phenomenon has been considered to be pathognomonic for McArdle disease, but we demonstrate that it can also be present in PGM1 deficiency. We show that severe loss of PGM1 activity causes blocked muscle glycogenolysis that mimics McArdle disease, but may also limit glycogen synthesis, which broadens the phenotypic spectrum of this disorder.

Topics: Adolescent; Biopsy; Exercise; Female; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type V; Glycogenolysis; Heart Rate; Humans; Lactates; Male; Muscle Fatigue; Muscle, Skeletal; Muscular Diseases; Oxidation-Reduction; Oxygen Consumption; Physical Exertion; Rhabdomyolysis; Skin

OBJECTIVE To characterize clinical findings for polysaccharide storage myopathy (PSSM) in warmblood horses with type 1 PSSM (PSSM1; caused by mutation of the glycogen synthase 1 gene) and type 2 PSSM (PSSM2; unknown etiology). SAMPLE Database with 3,615 clinical muscle biopsy submissions. PROCEDURES Reported clinical signs and serum creatine kinase (CK) and aspartate aminotransferase (AST) activities were retrospectively analyzed for horses with PSSM1 (16 warmblood and 430 nonwarmblood), horses with PSSM2 (188 warmblood and 646 nonwarmblood), and warmblood horses without PSSM (278). Lameness examinations were reviewed for 9 warmblood horses with PSSM2. Muscle glycogen concentrations were evaluated for horses with PSSM1 (14 warmblood and 6 nonwarmblood), warmblood horses with PSSM2 (13), and horses without PSSM (10 warmblood and 6 nonwarmblood). RESULTS Rhabdomyolysis was more common for horses with PSSM1 (12/16 [75%] warmblood and 223/303 [74%] nonwarmblood) and nonwarmblood horses with PSSM2 (221/436 [51%]) than for warmblood horses with PSSM2 (39/147 [27%]). Gait abnormality was more common in warmblood horses with PSSM2 (97/147 [66%]) than in warmblood horses with PSSM1 (1/16 [7%]), nonwarmblood horses with PSSM2 (176/436 [40%]), and warmblood horses without PSSM (106/200 [53%]). Activities of CK and AST were similar in warmblood horses with and without PSSM2. Muscle glycogen concentrations in warmblood and nonwarmblood horses with PSSM1 were significantly higher than concentrations in warmblood horses with PSSM2. CONCLUSIONS AND CLINICIAL RELEVANCE Rhabdomyolysis and elevated muscle glycogen concentration were detected in horses with PSSM1 regardless of breed. Most warmblood horses with PSSM2 had stiffness and gait abnormalities with CK and AST activities and muscle glycogen concentrations within reference limits.

Topics: Animals; Biopsy; Female; Glycogen; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Synthase; Horse Diseases; Horses; Male; Muscular Diseases; Mutation; Polysaccharides; Retrospective Studies; Rhabdomyolysis

Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, hepatic adenomas, and generalized myopathy. A naturally occurring canine model of GSD IIIa that mimics the human disease has been described, with progressive liver disease and skeletal muscle damage likely due to excess glycogen deposition. In the current study, long-term follow-up of previously described GSD IIIa dogs until 32 mo of age (n = 4) and of family-owned GSD IIIa dogs until 11 to 12 y of age (n = 2) revealed that elevated concentrations of liver and muscle enzyme (AST, ALT, ALP, and creatine phosphokinase) decreased over time, consistent with hepatic cirrhosis and muscle fibrosis. Glycogen deposition in many skeletal muscles; the tongue, diaphragm, and heart; and the phrenic and sciatic nerves occurred also. Furthermore, the urinary biomarker Glc4, which has been described in many types of GSD, was first elevated and then decreased later in life. This urinary biomarker demonstrated a similar trend as AST and ALT in GSD IIIa dogs, indicating that Glc4 might be a less invasive biomarker of hepatocellular disease. Finally, the current study further demonstrates that the canine GSD IIIa model adheres to the clinical course in human patients with this disorder and is an appropriate model for developing novel therapies.

Topics: Age Factors; Animals; Biomarkers; Disease Models, Animal; Disease Progression; Dog Diseases; Dogs; Female; Glycogen; Glycogen Storage Disease Type III; Hepatomegaly; Liver; Liver Cirrhosis; Male; Muscle, Skeletal; Muscular Diseases; Species Specificity; Urolithiasis

Given the diversity of autophagy targets and regulation, it is important to characterize autophagy in various cell types and conditions. We used a primary myocyte cell culture system to assay the role of putative autophagy regulators in the specific context of skeletal muscle. By treating the cultures with rapamycin (Rap) and chloroquine (CQ) we induced an autophagic response, fully suppressible by knockdown of core ATG genes. We screened D. melanogaster orthologs of a previously reported mammalian autophagy protein-protein interaction network, identifying several proteins required for autophagosome formation in muscle cells, including orthologs of the Rab regulators RabGap1 and Rab3Gap1. The screen also highlighted the critical roles of the proteasome and glycogen metabolism in regulating autophagy. Specifically, sustained proteasome inhibition inhibited autophagosome formation both in primary culture and larval skeletal muscle, even though autophagy normally acts to suppress ubiquitin aggregate formation in these tissues. In addition, analyses of glycogen metabolic genes in both primary cultured and larval muscles indicated that glycogen storage enhances the autophagic response to starvation, an important insight given the link between glycogen storage disorders, autophagy, and muscle function.

Topics: Animals; Autophagy; Cell Communication; Chloroquine; Drosophila melanogaster; Glycogen; GTPase-Activating Proteins; Larva; Muscle Cells; Muscle, Skeletal; Muscular Diseases; Phagosomes; Protein Interaction Maps; rab3 GTP-Binding Proteins; Sirolimus; Ubiquitin

Topics: Brain; Glycogen; Glycogen Storage Disease Type V; Humans; Muscle, Skeletal; Muscular Diseases

Topics: Animals; Autophagy; Glycogen; Muscular Diseases

Several myopathies are associated with defects in autophagic and lysosomal degradation of glycogen, but it remains unclear how glycogen is targeted to the lysosome and what significance this process has for muscle cells. We have established a Drosophila melanogaster model to study glycogen autophagy in skeletal muscles, using chloroquine (CQ) to simulate a vacuolar myopathy that is completely dependent on the core autophagy genes. We show that autophagy is required for the most efficient degradation of glycogen in response to starvation. Furthermore, we show that CQ-induced myopathy can be improved by reduction of either autophagy or glycogen synthesis, the latter possibly due to a direct role of Glycogen Synthase in regulating autophagy through its interaction with Atg8.

Topics: Amino Acid Sequence; Animals; Autophagy; Catalytic Domain; Chloroquine; Drosophila melanogaster; Drosophila Proteins; Glycogen; Glycogen Synthase; Glycogenolysis; Lysosomes; Molecular Sequence Data; Muscles; Muscular Diseases; Mutation, Missense; Phagosomes

RNA interference has emerged as a powerful technique to down-regulate gene expression. The lentiviral vector-mediated expression of small hairpin RNAs (shRNAs) from polymerase III promoters allows permanent down-regulation of a specific gene in a wide range of cell types both in vitro and in vivo. In this chapter, we describe a method permitting the expression of shRNA from lentiviral vectors in primary murine myogenic cells. We designed shRNAs targeted to the muscular glycogen synthase isoform (shGYS1), a highly regulated enzyme responsible for glycogen synthesis, in order to modulate the muscle glycogen biosynthetic pathway and to improve the phenotype in primary myogenic cells from a murine model of glycogen storage disease type II (GSDII). This method based on shRNA-mediated down-regulation could be applied to other muscular disorders to evaluate new therapeutic options.

Topics: Animals; Cells, Cultured; Gene Expression; Genetic Vectors; Glycogen; Glycogen Storage Disease Type II; Glycogen Synthase; Lentivirus; Membrane Glycoproteins; Mice; Muscular Diseases; Myoblasts; RNA Interference; RNA, Small Interfering; Viral Envelope Proteins

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common long-chain fatty acid oxidation defect presenting with heterogeneous clinical phenotypes. Dietary fat plays a crucial role in disease pathogenesis and fat restriction is a common treatment measure. We here investigate the hepatic and muscular effects of a fat-enriched and a fat-restricted diet.. VLCAD knock-out (KO) and wild-type (WT) mice are subjected to a fat-rich (10.6%), a fat-reduced (2.6%) or a regular mouse diet (5.1%) for 5 weeks. Analyses are performed at rest and after one hour exercise on a treadmill. Acylcarnitines in muscle as well as lipid and glycogen content in muscle and liver are quantified. Expression of genes involved in lipogenesis is measured by Real-Time-PCR.. At rest, VLCAD KO mice develop no clinical phenotype with all three diets, but importantly VLCAD KO mice cannot perform one hour exercise as compared to WT, this is especially apparent in mice with a fat-reduced diet. Moreover, changes in dietary fat content induce a significant increase in muscular long-chain acylcarnitines and hepatic lipid content in VLCAD KO mice after exercise. A fat-reduced diet up-regulates hepatic lipogenesis at rest. At the same time, muscular glycogen is significantly lower than in WT.. We here demonstrate that a fat-reduced and carbohydrate-enriched diet does not prevent the myopathic phenotype in VLCAD KO mice. An increase in dietary fat is safe at rest with respect to the muscle but results in a significant muscular acylcarnitine increase after exercise.

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Animals; Carnitine; Congenital Bone Marrow Failure Syndromes; Diet; Dietary Fats; Energy Metabolism; Glycogen; Lipid Metabolism; Lipid Metabolism, Inborn Errors; Lipids; Lipogenesis; Liver; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mitochondrial Diseases; Muscle, Skeletal; Muscular Diseases; Physical Exertion; Up-Regulation

Mammalian target of rapamycin complex 1 (mTORC1) is central to the control of cell, organ, and body size. Skeletal muscle-specific inactivation of mTORC1 in mice results in smaller muscle fibers, fewer mitochondria, increased glycogen stores, and a progressive myopathy that causes premature death. In mTORC1-deficient muscles, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), which regulates mitochondrial biogenesis and glucose homeostasis, is strongly down-regulated. Here we tested whether induction of mitochondrial biogenesis pharmacologically or by the overexpression of PGC-1α is sufficient to reverse the phenotype of mice deficient for mTORC1. We show that both approaches normalize mitochondrial function, such as oxidative capacity and expression of mitochondrial genes. However, they do not prevent or delay the progressive myopathy. In addition, we find that mTORC1 has a much stronger effect than PGC-1α on the glycogen content in muscle. This effect is based on the strong activation of PKB/Akt in mTORC1-deficient mice. We also show that activation of PKB/Akt not only affects glycogen synthesis but also diminishes glycogen degradation. Thus, our work provides strong functional evidence that mitochondrial dysfunction in mice with inactivated mTORC1 signaling is caused by the down-regulation of PGC-1α. However, our data also show that the impairment of mitochondria does not lead directly to the lethal myopathy.

Topics: Animals; Bezafibrate; Gene Expression Regulation; Glycogen; Male; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Knockout; Mice, Transgenic; Mitochondria; Mitochondria, Muscle; Models, Genetic; Multiprotein Complexes; Muscle, Skeletal; Muscular Diseases; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Proteins; TOR Serine-Threonine Kinases; Trans-Activators; Transcription Factors

The authors describe a 50-year-old man who was evaluated for a rigid spine syndrome with onset at age 15, and subsequent walking difficulties. Cardiac and pulmonary functions were normal. Deltoid biopsy revealed the presence of small vacuoles and increased glycogen with Periodic Acid Schiff staining in a limited number of fibers. Acid alpha-glucosidase staining was decreased in leucocytes, and genetic analysis identified the presence of two mutations in that gene. This observation suggests that Pompe disease should be considered in the differential diagnosis of rigid spine syndrome, even in patients without respiratory involvement or with a muscle biopsy showing only mild histopathological changes.

Topics: Age Factors; Age of Onset; alpha-Glucosidases; Biopsy; DNA Mutational Analysis; Gait Disorders, Neurologic; Glycogen; Glycogen Storage Disease Type II; Humans; Leukocytes; Male; Middle Aged; Mobility Limitation; Muscle, Skeletal; Muscular Diseases; Mutation; Periodic Acid-Schiff Reaction; Spinal Diseases; Spine

We consider recent developments in disorders affecting three areas of metabolism: glycogen, fatty acids, and the mitochondrial respiratory chain. Among the glycogenoses, new attention has been directed to defects of glycogen synthesis resulting in absence rather than excess of muscle glycogen ("aglycogenosis"). These include defects of glycogen synthetase and defects of glycogenin, the primer of glycogen synthesis. Considerable progress also has been made in our understanding of alterations of glycogen metabolism that result in polyglucosan storage. Among the disorders of lipid metabolism, mutations in the genes encoding two triglyceride lipases acting hand in hand cause severe generalized lipid storage myopathy, one associated with ichthyosis (Chanarin-Dorfman syndrome), the other dominated by juvenile-onset weakness. For the mitochondrial myopathies, we discuss the importance of homoplasmic mitochondrial DNA mutations and review the rapid progress made in our understanding of the coenzyme Q(10) deficiencies, which are often treatable.

Topics: Animals; Cell Nucleus; DNA; DNA, Mitochondrial; Fatty Acids; Glycogen; Humans; Lipid Metabolism; Metabolism, Inborn Errors; Mitochondrial Diseases; Mitochondrial Myopathies; Muscular Diseases; Mutation

In this study we examined a family of Quarter Horses with Polysaccharide Storage Myopathy (PSSM) with a dominant mutation in the skeletal muscle glycogen synthase (GYS1) gene. A subset of horses within this family had a more severe and occasionally fatal PSSM phenotype. The purpose of this study was to identify a modifying gene(s) for the severe clinical phenotype. A genetic association analysis was used to identify RYR1 as a candidate modifying gene. A rare, known equine RYR1 mutation, associated with malignant hyperthermia (MH), was found to segregate in this GYS1 PSSM family. Retrospective analysis of patient records (n=179) demonstrated that horses with both the GYS1 and RYR1 mutations had a more severe clinical phenotype than horses with the GYS1 mutation alone. A treadmill trial (n=8) showed that serum creatine kinase activity was higher and exercise intolerance greater in horses with both mutations compared to the GYS1 mutation alone.

Topics: Animals; DNA Mutational Analysis; Exercise Test; Exercise Tolerance; Female; Genetic Predisposition to Disease; Genetic Testing; Glycogen; Glycogen Storage Disease; Glycogen Synthase; Horse Diseases; Horses; Inheritance Patterns; Male; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Mutation; Pedigree; Phenotype; Retrospective Studies; Ryanodine Receptor Calcium Release Channel

Statins are commonly used drugs in the treatment of hypercholesterolaemia. There are many adverse effects of statins on skeletal muscle, but the underlying mechanisms remain unclear. In the present study, the effects of low dose (20 mg/kg) simvastatin, a lipophilic statin, on rat EDL muscle (extensor digitorum longus muscle) were investigated at the molecular level using FTIR (Fourier-transform infrared) spectroscopy. FTIR spectroscopy allows us rapid and sensitive determination of functional groups belonging to proteins, lipids, carbohydrates and nucleic acids simultaneously. The results revealed that simvastatin treatment induces a significant decrease in lipid, nucleic acid, protein and glycogen content. A significant increase in the lipid/protein and nucleic acid/protein ratios was also obtained with simvastatin treatment. Furthermore, an increase in lipid order and membrane fluidity was detected. A decrease in the bandwidth of the amide I band and shifting of the position of this band to higher frequency values in treated muscle indicates structural changes in proteins. Detailed secondary structure analysis of the amide I band revealed a significant increase in antiparallel and aggregated beta-sheet, random coil structure and a significant decrease in beta-sheet structure, which indicates protein denaturation.

Topics: Animals; Dose-Response Relationship, Drug; Down-Regulation; Fourier Analysis; Glycogen; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipid Metabolism; Male; Muscle Proteins; Muscle, Skeletal; Muscular Diseases; Nucleic Acids; Protein Denaturation; Protein Stability; Protein Structure, Secondary; Rats; Rats, Wistar; Simvastatin; Spectrophotometry, Infrared

Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype.. Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses.Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCalpha, VEGFalpha. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3beta) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1alpha) destabilization.. The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.

Topics: Animals; Female; Gene Expression Profiling; Gene Expression Regulation; Genotype; Glycogen; Horse Diseases; Horses; Hypoxia; Inflammation; Male; Mitochondria; Muscle, Skeletal; Muscular Diseases; Phenotype; Polysaccharides

Hexose-6-phosphate dehydrogenase (H6PD) is the initial component of a pentose phosphate pathway inside the endoplasmic reticulum (ER) that generates NADPH for ER enzymes. In liver H6PD is required for the 11-oxoreductase activity of 11beta-hydroxysteroid dehydrogenase type 1, which converts inactive 11-oxo-glucocorticoids to their active 11-hydroxyl counterparts; consequently, H6PD null mice are relatively insensitive to glucocorticoids, exhibiting fasting hypoglycemia, increased insulin sensitivity despite elevated circulating levels of corticosterone, and increased basal and insulin-stimulated glucose uptake in muscles normally enriched in type II (fast) fibers, which have increased glycogen content. Here, we show that H6PD null mice develop a severe skeletal myopathy characterized by switching of type II to type I (slow) fibers. Running wheel activity and electrically stimulated force generation in isolated skeletal muscle are both markedly reduced. Affected muscles have normal sarcomeric structure at the electron microscopy level but contain large intrafibrillar membranous vacuoles and abnormal triads indicative of defects in structure and function of the sarcoplasmic reticulum (SR). SR proteins involved in calcium metabolism, including the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), calreticulin, and calsequestrin, show dysregulated expression. Microarray analysis and real-time PCR demonstrate overexpression of genes encoding proteins in the unfolded protein response pathway. We propose that the absence of H6PD induces a progressive myopathy by altering the SR redox state, thereby impairing protein folding and activating the unfolded protein response pathway. These studies thus define a novel metabolic pathway that links ER stress to skeletal muscle integrity and function.

Topics: Animals; Calcineurin; Carbohydrate Dehydrogenases; Endoplasmic Reticulum; Enzyme Activation; Gene Deletion; Glycogen; Mice; Microscopy, Electron; Muscular Diseases; Mutation; NADP; Oligonucleotide Array Sequence Analysis; Protein Folding; RNA, Messenger; Signal Transduction

Muscle biopsies from chronic steroid (glucocorticoid) myopathy, non-steroid histochemical type-2 fiber atrophy, and muscle denervation patients were studied to determine if their glycogen contents, or enzymes involved in glycogenolysis and glycolysis might be related to their fiber atrophy.. Fast frozen muscle biopsies from the above patients and from patients later judged by histochemistry to be normal were assayed enzymatically for glycogen content, for enzymes involved in glycogenolysis, and for 6 of the enzymes involved in glycolysis.. All three groups of patients had glycogen content, but only the chronic steroid myopathy muscle had statistically less glycogen content than did normal human muscle. All 3 groups had statistically low mean values compared to normal muscles for glycogen phosphorylase activity. This suggests that the biosynthesis and phosphorolysis of glycogen are not involved in muscle fiber atrophy, and glucocorticoid administration does not activate muscle glycogen biosynthesis. Histochemical type-2 fiber atrophy muscles were low compared to normal muscles in three glycogenolysis enzyme activities plus four glycolysis enzyme activities. Muscles from denervation patients were low compared to normal muscles in three glycogenolysis enzyme activities plus five glycolysis enzyme activities. This suggests that muscle denervation may lower the rate of glycolysis enough to fail to provide sufficient pyruvate for mitochondrial ATP biosynthesis, resulting in insufficient protein biosynthesis in both fiber types.

Topics: Adult; Aged; Female; Glycogen; Glycogenolysis; Glycolysis; Humans; Male; Middle Aged; Muscle Denervation; Muscle, Skeletal; Muscular Atrophy; Muscular Diseases

Polyglucosan body disease (PBD) is a slowly progressive adult-onset glycogen storage disorder that typically affects upper and lower neurons. Myopathy, as a complication of PBD has been reported rarely and clinically manifests as chronic limb-girdle muscle weakness. We report an unusual case of PBD myopathy presenting as an asymmetric motor syndrome that clinically overlapped with amyotrophic lateral sclerosis, further expanding the phenotype of this disorder.

Topics: Amyotrophic Lateral Sclerosis; Diagnosis, Differential; Female; Glucans; Glycogen; Glycogen Storage Disease; Humans; Microscopy, Electron, Transmission; Middle Aged; Muscle Fibers, Skeletal; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Reflex, Abnormal

Muscle samples from 24 horses with polysaccharide storage myopathy were stained with periodic acid-Schiff (PAS) stain and were immunostained for ubiquitin. Abnormalities detected with PAS stain were coarse granular cytoplasmic aggregates of amylase sensitive glycogen, subsarcolemmal aggregates of glycogen, central amylase sensitive bodies, and a variety of subsarcolemmal to intracytoplasmic amylase resistant polyglucosan inclusions. All amylase resistant inclusions were positive for ubiquitin. Ubiquitin was also detected in many amylase sensitive inclusions. Based on morphologic findings and pattern of ubiquitin staining, a sequence of events, beginning with abnormal glycogen storage followed by ubiquitination and eventual development of amylase resistance, is proposed.

Topics: Amylases; Animals; Glucans; Glycogen; Glycogen Storage Disease; Horse Diseases; Horses; Immunohistochemistry; Inclusion Bodies; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Periodic Acid-Schiff Reaction; Species Specificity; Ubiquitin

To determine concentrations of proglycogen (PG), macroglycogen (MG), glucose, and glucose-6-phosphate (G-6-P) in skeletal muscle of horses with polysaccharide storage myopathy (PSSM) before and after performing light submaximal exercise.. 6 horses with PSSM and 4 control horses.. Horses with PSSM completed repeated intervals of 2 minutes of walking followed by 2 minutes of trotting on a treadmill until muscle cramping developed. Four untrained control horses performed a similar exercise test for up to 20 minutes. Serum creatine kinase (CK) activity was measured before and 4 hours after exercise. Concentrations of total glycogen (G(t)), PG, MG, G-6-P, free glucose, and lactate were measured in biopsy specimens of gluteal muscle obtained before and after exercise.. Mean serum CK activity was 26 times higher in PSSM horses than in control horses after exercise. Before exercise, muscle glycogen concentrations were 1.5, 2.2, and 1.7 times higher for PG, MG, and G(t), respectively, in PSSM horses, compared with concentrations in control horses. No significant changes in G(t), PG, MG, G-6-P, and lactate concentrations were detected after exercise. However, free glucose concentrations in skeletal muscle increased significantly in PSSM horses after exercise.. Analysis of the results suggests that glucose uptake in skeletal muscle is augmented in horses with PSSM after light exercise. There is excessive storage of PG and MG in horses with PSSM, and high concentrations of the 2 glycogen fractions may affect functional interactions between glycogenolytic and glycogen synthetic enzymes and glycosomes.

Topics: Animals; Biopsy; Creatine Kinase; Female; Glucose; Glucose-6-Phosphate; Glycogen; Glycogen Storage Disease; Horse Diseases; Horses; Lactic Acid; Male; Muscle, Skeletal; Muscular Diseases; Physical Conditioning, Animal

Muscle samples were obtained at necropsy from 225 horses and ponies 1 year of age or older. Samples were processed in routine manner and were stained with hematoxylin and eosin and with periodic acid-Schiff for glycogen. Sections were examined for abnormal glycogen content and amylase-resistant complex polysaccharide and for chronic myopathic change (excessive fiber size variation, increase in number of internal nuclei). A total of 101 horses and ponies with lesions of polysaccharide storage myopathy were identified. Age of affected horses ranged from one to 30 years, with a mean of 14.7 years. Mean age of nonaffected horses was 12 years. Incidence of polysaccharide storage myopathy varied depending on breed; Thoroughbreds had the lowest (27%) and draft-related horses had the highest (86%) incidence. Chronic myopathic changes were more severe in polysaccharide storage myopathy-affected horses than in nonaffected horses. Results of this study indicate that polysaccharide storage myopathy is a common disorder of many breeds of horses and ponies.

Topics: Animals; Carbohydrate Metabolism, Inborn Errors; Female; Glycogen; Horse Diseases; Horses; Incidence; Male; Muscle, Skeletal; Muscular Diseases; Species Specificity

This study was designed to investigate whether horses with clinical signs of back pain due to suspected soft tissue injuries were affected by polysaccharide storage myopathy (PSSM). Diagnosis of PSSM in muscle biopsies obtained from the M. longissimus lumborum of 5 showjumpers and 4 dressage horses with a history of back pain is reported. M. longissimus lumborum biopsies of these horses were characterised histopathologically and in 3/9 cases also by electron microscopy. Observations were compared with M. gluteus biopsies of the same horses, and with M. gluteus biopsies obtained from 6 Standardbreds with recurrent exertional rhabdomyolysis and from 6 healthy trotters. M. longissimus biopsies from horses with back pain showed pathognomonic signs of PSSM, i.e. high glycogen and/or abnormal complex amylase-resistant polysaccharide deposits. Similar features were found in M. gluteus biopsies of the same horses. Sections of horses with rhabdomyolysis had increased PAS stain when compared with healthy horses, but did not show amylase-resistant material. Qualitative observations were corroborated by quantitative histochemistry (optical densities) of sections stained with PAS and amylase PAS. This study demonstrated the presence of PSSM in the M. longissimus of showjumpers and dressage horses with back pain and indicates that epaxial muscle biopsy is an option in diagnosing back problems in horses when clinical examination and imaging techniques do not provide a precise diagnosis.

Topics: Amylases; Animals; Back Pain; Biopsy; Carbohydrate Metabolism, Inborn Errors; Diagnosis, Differential; Glycogen; Horse Diseases; Horses; Microscopy, Electron; Muscle, Skeletal; Muscular Diseases; Polysaccharides; Rhabdomyolysis

Skeletal muscle samples from 38 draft horse-related animals 1-23 years of age were evaluated for evidence of aggregates of glycogen and complex polysaccharide characteristic of equine polysaccharide storage myopathy (EPSSM). Cardiac muscle from 12 of these horses was also examined. Antemortem serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) from 9 horses with EPSSM and 5 horses without EPSSM were compared. Skeletal muscle from 17 horses contained inclusions of periodic acid-Schiff (PAS)-positive, amylase-resistant complex polysaccharide. Similar inclusions were also present in the cardiac muscle of 1 horse. A vacuolar myopathy with aggregates of PAS-positive, amylase-sensitive glycogen was seen in 8 other horses, and these findings are also considered diagnostic for EPSSM. Antemortem serum activities of CK and AST were often higher in EPSSM horses than in horses without EPSSM. Using the presence of amylase-resistant complex polysaccharide as the criterion for diagnosis of EPSSM, the incidence in this population was 45%. Inclusion of horses with aggregates of glycogen but no amylase-resistant complex polysaccharide as representative of the range of pathologic findings in horses with EPSSM resulted in a 66% incidence in this population.

Topics: Amylases; Animals; Autopsy; Carbohydrate Metabolism; Carbohydrate Metabolism, Inborn Errors; Female; Glycogen; Horse Diseases; Horses; Incidence; Male; Muscle, Skeletal; Muscular Diseases

The purpose of this study was to determine whether greater body fat mass (FM) relative to lean mass would result in more severe muscle damage and greater decrements in leg strength after downhill running. The relationship between the FM-to-fat-free mass ratio (FM/FFM) and the strength decline resulting from downhill running (-11% grade) was investigated in 24 male runners [age 23.4 +/- 0.7 (SE) yr]. The runners were divided into two groups on the basis of FM/FFM: low fat (FM/FFM = 0.100 +/- 0.008, body mass = 68.4 +/- 1.3 kg) and normal fat (FM/FFM = 0.233 +/- 0.020, body mass = 76.5 +/- 3.3 kg, P < 0.05). Leg strength was reduced less in the low-fat (-0.7 +/- 1.3%) than in the normal-fat individuals (-10.3 +/- 1.5%) 48 h after, compared with before, downhill running (P < 0.01). Multiple linear regression analysis revealed that the decline in strength could be predicted best by FM/FFM (r2 = 0.44, P < 0.05) and FM-to-thigh lean tissue cross-sectional area ratio (r2 = 0.53, P < 0.05), with no additional variables enhancing the prediction equation. There were no differences in muscle glycogen, creatine phosphate, ATP, or total creatine 48 h after, compared with before, downhill running; however, the change in muscle glycogen after downhill running was associated with a higher FM/FFM (r = -0.56, P < 0.05). These data suggest that FM/FFM is a major determinant of losses in muscle strength after downhill running.

Topics: Adenosine Triphosphate; Adult; Anaerobic Threshold; Body Composition; Creatine; Creatine Kinase; Glycogen; Humans; Lactic Acid; Leg; Male; Muscle, Skeletal; Muscular Diseases; Oxygen Consumption; Phosphocreatine; Physical Fitness; Regression Analysis; Running

To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose.. 6 horses with PSSM and 10 healthy (control) horses.. Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration.. Peak glucose concentrations during IVGTT were similar for both groups of horses, but rate of glucose clearance was 1.5 times faster in horses with PSSM than in controls. Moreover, circulating concentrations of insulin before and after glucose injection were lower in the PSSM group. Blood glucose concentrations from minute 90 to minute 300 of the OGTT were lower in horses with PSSM than in controls. The MITT resulted in acute decreases in blood glucose concentrations in both groups of horses; however, horses with PSSM sustained low blood glucose concentrations for more than 3 hours after insulin injection, whereas blood glucose concentrations in controls returned to baseline values within 2 hours.. Quarter Horses with PSSM have enhanced cellular uptake of glucose that may be, in part, caused by an increased sensitivity to insulin.. Horses with PSSM have an increased rate of glucose clearance in response to insulin secretion. Thus, diets low in soluble carbohydrate may be the most effective way to decrease glycogen accumulation in skeletal muscle of these horses.

Topics: Animals; Blood Glucose; Female; Glucose; Glucose Tolerance Test; Glycogen; Glycogen Storage Disease; Horse Diseases; Horses; Insulin; Male; Muscle, Skeletal; Muscular Diseases; Polysaccharides; Rhabdomyolysis

This report demonstrates that a single intravenous administration of a gene therapy vector can potentially result in the correction of all affected muscles in a mouse model of a human genetic muscle disease. These results were achieved by capitalizing both on the positive attributes of modified adenovirus-based vectoring systems and receptor-mediated lysosomal targeting of enzymes. The muscle disease treated, glycogen storage disease type II, is a lysosomal storage disorder that manifests as a progressive myopathy, secondary to massive glycogen accumulations in the skeletal and/or cardiac muscles of affected individuals. We demonstrated that a single intravenous administration of a modified Ad vector encoding human acid alpha-glucosidase (GAA) resulted in efficient hepatic transduction and secretion of high levels of the precursor GAA proenzyme into the plasma of treated animals. Subsequently, systemic distribution and uptake of the proenzyme into the skeletal and cardiac muscles of the GAA-knockout mouse was confirmed. As a result, systemic decreases (and correction) of the glycogen accumulations in a variety of muscle tissues was demonstrated. This model can potentially be expanded to include the treatment of other lysosomal enzyme disorders. Lessons learned from systemic genetic therapy of muscle disorders also should have implications for other muscle diseases, such as the muscular dystrophies.

Topics: Adenoviridae; alpha-Glucosidases; Animals; Cytomegalovirus; Genes, pol; Genetic Therapy; Genetic Vectors; Glycogen; Glycogen Storage Disease Type II; Humans; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Muscular Diseases; Promoter Regions, Genetic

A severe myopathy leading to death or euthanasia was identified in 4 Belgian and 4 Percheron draught horses age 2-21 years. Clinical signs ranged from overt weakness and muscle atrophy in 2 horses age 2 and 3 years, to recumbency with inability to rise in 6 horses age 4-21 years. In 5 horses there was mild to severe increases in muscle enzyme levels. Clinical diagnoses included equine motor neuron disease (2 horses), post anaesthetic myopathy (2 horses), exertional myopathy (2 horses), myopathy due to unknown (one horse), and equine protozoal myelitis (one horse). Characteristic histopathology of muscle from affected horses was the presence of excessive complex polysaccharide and/or glycogen, revealed by periodic acid-Schiff staining in all cases and by electron microscopy in one case. Evaluation of frozen section histochemistry performed on 2 cases indicated that affected fibres were Type 2 glycolytic fibres. Subsarcolemmal and intracytoplasmic vacuoles were most prominent in 3 horses age 2-4 years, and excessive glycogen, with little or no complex polysaccharide, was the primary compound stored in affected muscle in these young horses. Myopathic changes, including fibre size variation, fibre hypertrophy, internal nuclei, and interstitial fat infiltration, were most prominent in 5 horses age 6-21 years, and the accumulation of complex polysaccharide appeared to increase with age. Mild to moderate segmental myofibre necrosis was present in all cases.

Topics: Animals; Atrophy; Female; Glycogen; Glycogen Storage Disease; Histocytochemistry; Horse Diseases; Horses; Hypertrophy; Male; Microscopy, Electron, Scanning Transmission; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Necrosis; Polysaccharides

Topics: Adult; Female; Glycogen; Humans; Middle Aged; Muscle, Skeletal; Muscular Diseases; Prednisone

Muscle biopsies from three patients with cardiomyopathy, mental retardation and increased serum creatine kinase levels revealed scattered fibers with tiny intracytoplasmic vacuoles containing basophilic and acid phosphatase-positive material and slightly increased amounts of PAS-positive granules. These findings are consistent with those seen in the so-called lysosomal glycogen storage disease with normal acid maltase. In addition to the vacuoles, there were occasional folds or indentations in the sarcolemma which were connected to the membrane enclosing the vacuoles. These membranes were well demonstrated histochemically by the nonspecific esterase and acetylcholinesterase stains. On electron microscopy, most of the vacuoles were bounded by membranes with basal lamina. The vacuolar membrane stained positively with antibodies raised to dystrophin, dystrophin-associated glycoproteins, laminin and type 4 collagen, and it was identical to the sarcolemma and its basal lamina. Therefore, the membrane abnormality which causes sarcolemmal folding is probably critical to understanding the pathomechanism of this disease.

Topics: Adolescent; Adult; Basement Membrane; Biopsy; Cardiomyopathies; Cell Membrane; Dystrophin; Glycogen; Humans; Immunohistochemistry; Intellectual Disability; Male; Microscopy, Electron; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Sarcolemma; Staining and Labeling; Vacuoles

A case of an unusual congenital myopathy is reported. The boy presented at birth with generalized muscular hypotonia and dysmorphic features. Muscle biopsy at the age of 10 years revealed focal areas with decreased ATPase activity and variable oxidative enzyme activity. There was only one type II fiber in the whole section. 22.5% of fibers had central nuclei, sometimes with radial arrangement of the intermyofibrillary network. Focal lesions displayed strong desmin and weak vimentin immunoreactivity. On electron microscopic examination normal sarcomeres were focally disrupted and mitochondria were absent from these areas; the normal structure was replaced by numerous fragments of sarcoplasmic reticulum, filamentous material, scattered glycogen particles, and the Z-line was replaced by irregular longitudinal streaks of electron-dense fibrillar material. We classify this case as a congenital myopathy with focal loss of cross striations.

Topics: Abnormalities, Multiple; Adenosine Triphosphatases; Desmin; Glycerolphosphate Dehydrogenase; Glycogen; Humans; Immunohistochemistry; Male; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle Hypotonia; Muscle, Skeletal; Muscular Diseases; Myofibrils; NADH Tetrazolium Reductase; Vimentin

We report a family with McArdle's disease with several affected individuals in two generations. This unusual pedigree for an autosomal recessive disease is explained by the existence of manifesting heterozygotes in the maternal line. The presence of symptoms in heterozygotes seems to be due to a decrease in myophosphorylase activity below a critical threshold, ranging between 30% and 45% of normal mean value. The occurrence of several manifesting heterozygotes in the maternal line only can be explained by compound heterozygosity of a defective allele and a pseudodeficient allele for myophosphorylase, or by a genetic factor which regulates the phenotypic expression of the gene.

Topics: Adolescent; Adult; Densitometry; Electrophoresis, Polyacrylamide Gel; Female; Glycogen; Glycogen Storage Disease Type V; Heterozygote; Humans; Italy; Male; Muscles; Muscular Diseases; Pain; Phenotype; Phosphorylase a

Muscular glycogenosis is a disease resulting from genetical abnormalities altering an enzyme which is involved in glycogen metabolism. In addition to disorders of glycogenosis and glycolysis, there are other pathological processes such as alpha-glycosidase deficiency and diseases associated with abnormal polysaccharide structure. A short review of the various diseases with their particular features is reported.

Topics: Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VII; Glycolysis; Humans; Muscles; Muscular Diseases

Chronic ethanol feeding in the rat is associated with a skeletal myopathy involving primarily type-II muscle fibres, which is recognised to be mediated via a specific impairment in protein turnover. This paper investigates whether the cause of this myopathy may be related to abnormalities in carbohydrate and lipid metabolism in different muscles. [U-14C]Glucose metabolism was examined in two muscles with different fibre compositions, the extensor digitorum longus (EDL) muscle, which contains predominantly type-II muscle fibres, and the soleus muscle, which is composed primarily of type-I muscle fibres. Feeding on the ethanol-supplemented Lieber-DeCarli liquid diet for 2 or 6 weeks was associated with profound disturbances in glucose metabolism in both EDL and soleus muscles, particularly in relation to rates of glycogen and alanine formation. We discuss the importance of these metabolic changes in relation to the genesis of chronic alcoholic skeletal myopathy.

Topics: Animals; Ethanol; Glucose; Glycogen; Lipid Metabolism; Male; Muscles; Muscular Diseases; Organ Size; Rats; Rats, Wistar; Time Factors; Triglycerides

A 21-year-old man with childhood-onset mental retardation, non-obstructive hypertrophic cardiomyopathy, and vacuolar myopathy is presented. A histopathological study of biopsied skeletal muscle showed lysosomal glycogen storage mimicking acid maltase deficiency, but biochemical analysis showed normal acid alpha-glucosidase activity. Glycogenosomes were also recognized in endothelial cells on electronmicroscopic examination of biopsied skeletal muscle. Magnetic resonance imaging (MRI) findings in the head revealed the involvement of the central nervous system. This is a new type of lysosomal glycogen storage disease with multisystemic involvement. The specific biochemical defect in this disorder remains to be elucidated.

Topics: Adult; alpha-Glucosidases; Autophagy; Brain; Cardiomyopathies; Glycogen; Glycogen Debranching Enzyme System; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Muscles; Muscular Diseases; Syndrome; Vacuoles

Prolonged exposure (4 weeks) to 6.72 ppb of the organochlorine insecticide endosulfan induced disturbances in the blood and organ chemistry values of a common fish, Barbus conchonius. In blood the total lipids, cholesterol, and proteins were decreased in comparison to unexposed controls, while the free fatty acids (FFA), glucose, total phosphorus, and lactate were increased. Total lipids, FFA, and proteins were augmented in liver; cholesterol, in liver and ovary; and phosphorus and glycogen, in skeletal muscles. Compared to the controls, a decrease was seen in the total lipids (skeletal muscles and ovary), glycogen (liver, brain, and heart), and cholesterol (testes). Hyperlipemia, hyperproteinemia, and hyperlactemia persisted during a recovery period of 1 week in clean water following endosulfan poisoning.

Topics: Animals; Blood Glucose; Blood Proteins; Body Weight; Cholesterol; Endosulfan; Fatty Acids, Nonesterified; Fishes; Glucose; Glycogen; Lactates; Lipid Metabolism; Lipids; Liver; Muscular Diseases; Organ Size; Phosphorus; Proteins

The symptoms of a myopathy permanently affecting limb girdle muscles are reported in a 31-year-old woman who has been presenting an exertional muscle pain syndrome with myoglobinuria for 20 years. Investigations revealed a slightly decreased utilization of glycogen in muscle, while its storage affected only rare type 2 fibers. Active phosphorylase was undetectable and phosphorylase b kinase activity was clearly decreased in muscle cells, but normal in erythocytes, lymphocytes and cultured fibroblasts.

Topics: Adult; Atrophy; Female; Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Microscopy, Electron; Muscles; Muscular Diseases; Pain; Phosphorylase b; Phosphorylase Kinase; Physical Exertion; Syndrome

A case of 25-year-old woman with glycogen storage myopathy is reported here. She was hospitalized for acute heart failure after alcohol drinking. The electrocardiogram on admission showed marked ST elevation. Laboratory data showed elevated levels of serum myogenic enzymes but no rise in cardiomyogenic enzyme: CK 3862 IU/l CK-MB 35 IU/l, LDH 427 IU/l, GOT 203 IU/l. After several days, she recovered from acute heart failure and could walk without supporting. ST elevation in ECG and elevated myogenic enzymes were also normalized. The occurrence of acute myocardial infarction was ruled out because a coronary angiogram and 99 Tcm scintigram were normal. Physical examination revealed proximal muscular weakness and mental retardation (WAIS, total 72). Venous lactate response was normal after semi-ischemic forearm exercise. PAS staining of muscle specimen showed an excess deposit of glycogen. Ragged-red fibers were not seen on Gomori-trichrome stain. By electron microscopy, a large amount of glycogen particles were demonstrated in the subsarcolemma, but there were no abnormal mitochondrial changes. Biochemical analysis showed accumulation of glycogen in muscles: 28.7 mg/g muscle (normal 11.4 +/- 4.2 mg/g muscle). The activities of enzyme in the pathway of glycogen and glycogenosis (alpha-glucosidase, amylo-1,6-glucosidase, phosphorylase a, phosphorylase kinase, phosphofructokinase, etc.) were within normal limits. The spectrum of glycogen iodine complex was normal. Our case was different from any type of muscle glycogen storage disease previously reported. The etiology of an excess of glycogen deposit in muscles is unknown.

Topics: Acute Disease; Adult; alpha-Glucosidases; Female; Glycogen; Glycogen Storage Disease; Heart Failure; Humans; Muscles; Muscular Diseases

Morphological changes are shown in the muscle biopsy specimens of an 8-year-old girl who suffered from a triosephosphate isomerase (TPI) deficiency, resulting in a chronic, nonspherocytic, hemolytic anemia, mental retardation and neuromuscular impairment. The newly introduced enzyme histochemical reaction for TPI demonstrated a total lack of histochemically detectable enzyme activity, whereas biochemical analysis of muscle tissue revealed less than 10% of the normal enzyme activity. Electron microscopy showed a degenerative myopathy with an increase in the amount of intracellular glycogen. Additionally, mitochondrial changes within the muscle fibers were observed to be similar to those in mitochondrial myopathies. The disturbed balance between glycerin-aldehyde phosphate and dihydroxyacetone phosphate, due to the deficiency of the TPI enzyme, is interpreted as the biochemical background of an impaired electron transport across the mitochondrial membrane, resulting in the coexistence of an impaired glycolytic pathway and an impaired mitochondrial metabolism of muscle cells.

Topics: Carbohydrate Epimerases; Child; Female; Glycogen; Humans; Intellectual Disability; Mitochondria; Muscular Diseases; Triose-Phosphate Isomerase

In addition to the infantile lethal form of glycogen storage disease with cardiomyopathy (GSD Type IIa, Pompe disease) 1,4 glucosidase or acid maltase deficiency has been reported in a few children and adults (GSD Type IIb or IIc) erroneously thought to have muscular dystrophies. The clinical heterogeneity of the muscle involvement in these latter cases is illustrated in a 12-year-old boy presenting with a right lumbar mass, growth retardation, muscular weakness including difficulty in walking, and marked elevations of muscle and liver enzymes. Light- and electron-microscopic examination of specimens from the lumbar mass, apparently normal skeletal muscle and liver, showed typical changes consistent with the biochemical and enzymatic features of acid maltase deficiency. GSD Type IIb and IIc are more frequent than suspected, may present as local pseudohypertrophy and should be considered in patients with progressive muscle disease and abnormal serum enzymes.

Topics: alpha-Glucosidases; Back; Child; Diagnosis, Differential; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Liver Diseases; Male; Muscular Diseases

Crystalloid bodies in skeletal muscle fibers have been described in myopathic and non-myopathic conditions. They have been interpreted as viral, glycogen, protein-glycogen complex, artifacts and of unknown nature. This report described similar crystalloid bodies in the postmortem muscle samples of two patients with hypothyroid myopathy. The crystalloid bodies were preferentially located in the I band and Z line region and in the subsarcolemmal region closely associated with lipofuscin. Some were present within basophilic bodies. They were formed by parallel filaments of 6-10 nm beaded periodically by electron-dense particles of 10-18 nm in a lattice, hexagonal or parallel-ripple pattern. Merging of filaments of crystalloid bodies into actin filaments of the I band was noted. The electron-dense particles stained strongly with periodic acid-thiocarbohydrazide-silver proteinate method for polysaccharides and were unaffected or partially digested by diastase treatment on the ultrathin sections. The filamentous component was neither stained for polysaccharides nor digested by diastase treatment. It is suggested that crystalloid bodies of muscle fibers are composed of two distinct subunits with particles of glycogen complex attached to filaments of unknown nature.

Topics: Amylases; Crystallization; Female; Glycogen; Histocytochemistry; Humans; Hypothyroidism; Inclusion Bodies; Microscopy, Electron; Middle Aged; Muscles; Muscular Diseases; Polysaccharides

Physical fitness through exercise is the rage of today. Almost everybody is indulging in various forms of exercise from weight lifting to marathons. These regimens presuppose a normal muscle metabolism. However, a significant number of so-called normals end up with the symptoms of cramps, fatigue, and, in advanced cases, myoglobinuria. Exercise forms the mainstay of rehabilitation of patients with neurologic disorders manifesting as paresis or paralysis, and certain rheumatologic or metabolic problems are also handled via the medium of exercise therapy. It is, thus, imperative that there should be a clear understanding of normal muscle composition and metabolic responses. We will summarize the histology, histochemistry, physiology and metabolic responses of normal muscle to exercise and put this information in perspective in the light of various muscle disorders.

Topics: Adenosine Triphosphatases; Calcium; Carnitine; Carnitine O-Palmitoyltransferase; Female; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Lipid Metabolism, Inborn Errors; Male; Muscle Contraction; Muscles; Muscular Diseases; Physical Exertion; Potassium

Topics: Adult; Age Factors; alpha-Glucosidases; Female; Glucan 1,4-alpha-Glucosidase; Glucosidases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Lysosomes; Motor Neurons; Muscles; Muscular Diseases; Neuromuscular Diseases; Vacuoles

Metabolism of triceps, pectoralis (in the vicinity of tumor) and gastrocnemius (away from the tumor) muscles in Swiss albino mice bearing adenocarcinoma has been studied histochemically with regard to content of glycogen, lipids, phosphorylase, aldolase, lipase, succinate dehydrogenase and cytochrome oxidase in the constituent fibres. At 9-10 weeks after transplantation of adenocarcinoma, a negligible glycogen content and decreased phosphorylase and aldolase activities are observed in the white, intermediate and red fibre types in the three muscles. Hypertrophy of fibres and occurrence of targetoid fibres is distinct in the muscles of tumor-bearing mice. The red fibres demonstrate a general loss of lipids, lipase, succinate dehydrogenase and cytochrome oxidase whereas the hypertrophied fibres reveal intense localization of these parameters in their central zones. The results indicate that a decline in glycogenolysis, glycolysis, lipolysis and oxidative metabolism in the various fibre types may contribute to the muscle weakness and muscle wasting in the adenocarcinoma-bearing mice.

Topics: Adenocarcinoma; Animals; Electron Transport Complex IV; Fructose-Bisphosphate Aldolase; Glycogen; Glycolysis; Histocytochemistry; Lipase; Lipolysis; Mice; Mice, Inbred Strains; Muscles; Muscular Diseases; Neoplasm Transplantation; Oxidation-Reduction; Phosphorylases; Succinate Dehydrogenase

Topics: alpha-Glucosidases; Bisphosphoglycerate Mutase; Cells, Cultured; Glycogen; Glycogen Debranching Enzyme System; Humans; L-Lactate Dehydrogenase; Mucolipidoses; Muscular Diseases; Phosphofructokinase-1; Phosphoglycerate Kinase; Phosphorylases

The capacity for glycolysis in muscle biopsies obtained from long-term heavy alcohol drinking patients has been compared with tissue from control subjects by assay in vitro of the total activities of glycogen phosphorylase, phosphofructokinase and fructose 1,6-bisphosphatase, key regulatory enzymes in the anaerobic glycolytic pathway. Biopsies from 13 of 22 patients had type II fibre atrophy, and the activities of all three enzymes were reduced in these biopsies, when expressed in terms of DNA content, the most striking reduction being in phosphofructokinase activity. The amount of glycogen in the tissue correlated closely with these enzyme activities and was slightly lower in the most atrophic tissue, when expressed in terms of DNA content. The activities of acid and neutral alpha-glucosidases were similar in biopsies from control subjects and patients with various severities of alcohol myopathy. The reduced activities are consistent with a reduced proportion of type II fibre muscle mass in these patients, and suggest that there may be a reduced capacity for glycolysis with resultant reduced lactate production. Whether the changes in enzyme activities are primary to the selective atrophy remains to be established.

Topics: Adult; Aged; Alcoholism; alpha-Glucosidases; Female; Fructose-Bisphosphatase; Glycogen; Glycolysis; Humans; Male; Middle Aged; Muscles; Muscular Diseases; Phosphofructokinase-1; Phosphorylases

Topics: Adenine Nucleotides; Animals; Cell Membrane; Creatine Kinase; Energy Metabolism; Glucosephosphates; Glycogen; Mitochondria, Muscle; Muscles; Muscular Diseases; Myofibrils; Oxygen Consumption; Phosphates; Phosphocreatine; Phosphorylation; Rats; Rats, Inbred Strains; Time Factors

The clinical course of metabolic myopathies is dominated by progressive muscle weakness and wasting or aching contraction and recurrent rhabdomyolysis with intense exercise. Vacuolar muscle fibre degeneration is the leading pathological finding on routine histological examination. For further characterization of those histologically empty looking vacuoles, histochemistry and electron microscopy are employed. Increase of glycogen, lipid droplets or mitochondria can often be demonstrated and indicate the need for subsequent biochemical identification of the underlying metabolic defect. Some other metabolic myopathies that cause recurrent rhabdomyolysis lack myopathological abnormalities. These can only be diagnosed biochemically, but additional new histochemical screening methods might be helpful.

Topics: Biopsy; Contracture; Glycogen; Glycogen Storage Disease; Humans; Lipid Metabolism; Lipid Metabolism, Inborn Errors; Microscopy, Electron; Mitochondria, Muscle; Muscle Hypotonia; Muscles; Muscular Atrophy; Muscular Diseases; Rhabdomyolysis; Vacuoles

Metabolic myopathies are a rare group of disorders. These myopathies reveal a varying severity of a proximal, distal or generalized muscular involvement indicating a progressive myopathy or recurrent episodes of weakness, pain, cramps and stiffness combined with exercise. Some important disorders and their biochemical defects are described. Particular attention is paid to helpful biochemical investigative methods.

Topics: Enzymes; Glycogen; Glycogen Storage Disease; Humans; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Mitochondria, Muscle; Muscles; Muscular Diseases; Neuromuscular Diseases

Topics: Adult; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type III; Humans; Hypertrophy; Male; Muscles; Muscular Diseases; Peripheral Nerves; Peripheral Nervous System Diseases

Progressive muscle weakness in acid maltase deficiency (AMD) is associated with intralysosomal accumulation of glycogen and altered myofibrillar morphology. A rapid fall in circulating branched chain amino acids after protein ingestion in a child with AMD suggested that increased net muscle protein catabolism may play a part in the pathogenesis of this condition. To reduce this muscle catabolism, the patient was treated with a high-protein diet for 12 months. This has reversed the weakness and wasting, with improvement in muscle function, exercise tolerance, and growth.

Topics: Amino Acids, Branched-Chain; Child, Preschool; Dietary Proteins; Glucan 1,4-alpha-Glucosidase; Glucosidases; Glycogen; Humans; Male; Muscles; Muscular Diseases

Ten cases of myopathy caused by glycogen storage diseases of type II, III, and V, and phosphorylase b kinase deficiency are reported. So-called "abnormal lysosomes" or glycogenosomes which contain abundant glycogen were found in cases of type II, and in some numbers, in cases of type III, and in one case of phosphorylase b kinase deficiency which revealed a moderate decrease in debranching enzyme (amylo-1,6-glucosidase) activity. In these cases of type III and phosphorylase b kinase deficiency, the glycogenosomes are formed through deposition of abnormal glycogen (limit dextrin structure glycogen).

Topics: Adolescent; Adult; Biopsy; Child, Preschool; Female; Glycogen; Glycogen Storage Disease; Humans; Infant; Lysosomes; Male; Microscopy, Electron; Middle Aged; Muscles; Muscular Diseases; Phosphorylase Kinase

Steroids are so commonly prescribed for so many conditions that physicians tend to become somewhat cavalier in their use. With drug therapy of any type, however, this tendency can lead to trouble. Steroid myopathy, as occurs in Cushing's syndrome. Can develop with steroid therapy and can cause irreversible atrophy if not detected and treated early.

Topics: Adrenal Cortex Hormones; Drug Administration Schedule; Glycogen; Humans; Muscular Diseases; Oxidation-Reduction; Protein Biosynthesis; Steroids, Fluorinated

A girl with congenital limb weakness, mental retardation, and corneal ulceration died with respiratory insufficiency at age 4 years. Histochemistry of muscle biopsy showed only nonspecific myopathy, but electronmicroscopy revealed subsarcolemmal and intramyofibrillar accumulation of glycogen. Biochemical studies showed increased glycogen content of muscle with lack of phosphofructokinase. Phosphorylase b kinase activity was about 30% of normal. The relationship of the double enzyme deficiency to this unusual clinical picture is unclear.

Topics: Biopsy; Child, Preschool; Female; Glycogen; Glycogen Storage Disease; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Muscles; Muscular Diseases; Phosphofructokinase-1; Phosphorylase Kinase

Muscle cultured from two adults with debrancher deficiency myopathy showed abnormal glycogen deposits by electron microscopy. Glycogen debranching activity was markedly decreased, but phosphorylase activity was normal. Lack of glycogen debranching activity in muscle cultures from debrancher-deficient patients contrasts with the presence of a fetal isoenzyme of phosphorylase in muscle cultured from patients with McArdle disease and suggests that the genetic control of the debranching enzyme does not change during muscle development.

Topics: Adult; Culture Techniques; Female; Fibroblasts; Glucosyltransferases; Glycogen; Glycogen Debranching Enzyme System; Histocytochemistry; Humans; Male; Muscles; Muscular Diseases

Topics: Atrophy; Biopsy; Glycogen; Histological Techniques; Muscles; Muscular Diseases; Muscular Dystrophies

Topics: Carnitine; Glycogen; Humans; Infant; Lactates; Lipid Metabolism; Male; Mitochondria, Muscle; Muscular Diseases

We analyzed clinical, histological and biochemical findings in 10 patients with glycogen storage disease in skeletal muscle. Four patients were deficient in acid-alpha-glucosidase (Glycogenosis type II), three of them with late infantile onset and one patient adult form. Five patients, two of them siblings, were deficient in myophosphorylase (glycogenosis type V, McArdle's disease). One patient was a newborn with phosphofructokinase deficiency (glycogenosis type VII, Tarui's disease). Of the study of our cases we would like to outline the following features: in the glycogenosis type II the deposit is fundamentally intralysosomal in the late infantile form, storage of mucopolysaccharides and deposit in interstitial fibroblasts were found, while in the adult form glycogen storage is minimal. In the glycogenosis type V the storage of glycogen is free and of a small amount. In two patients we have observed enzymatic activity in regenerating fibres. In glycogenosis type VII the storage is free, of considerable quantity and the interstitial cells are also affected; no storage is observed in the satellite cells.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VII; Humans; Male; Muscles; Muscular Diseases

A 25-year-old woman with a non-familial congenital nonprogressive myopathy was found to have atypical core-like lesions in type 1 muscle fibers. Typical core lesions (approximately 13 micrometers in diameter) and smaller, PAS positive (4.1 micrometers in diameter) atypical core were associated with a predominant type 1 fibre myopathy. A specific deficiency of fructose 1, 6-diphosphatase was found with normal values for nine other muscle glycolytic and mitochondrial marker enzymes. The data provide evidence for a specific muscle enzyme deficiency in a patient with atypical central core disease.

Topics: Adenosine Triphosphatases; Adult; Female; Fructose-1,6-Diphosphatase Deficiency; Fructose-Bisphosphatase; Glycogen; Histocytochemistry; Humans; Muscles; Muscular Diseases; Myofibrils; NADH Tetrazolium Reductase

During the past nine years 10 patients with the adult form of acid maltase deficiency have been observed at the Mayo Clinic. Three of the adults presented with respiratory failure. In all three the respiratory manifestations dominated the clinical picture and the cause of the respiratory failure (muscle weakness) and the underlying myopathy (glycogen storage disease) were initially unsuspected. Careful evaluation of the respiratory function tests, including the maximal static respiratory pressures, electromyographic examination and histochemical and biochemical studies of muscle biopsy specimens eventually led to the correct diagnosis.

Topics: Adult; Electromyography; Female; Glucan 1,4-alpha-Glucosidase; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Male; Middle Aged; Muscles; Muscular Diseases; Respiratory Function Tests; Respiratory Insufficiency

A 25-month-old girl had proximal myopathy, increased blood lactate and pyruvate concentrations, and transient ketoacidosis. Muscle biopsy revealed vacuolar myopathy with accumulation of both lipid and glycogen. Electronmicroscopy also showed abnormalities in the shape, size, and internal structure of muscle mitochondria. Carnitine content of skeletal muscle was reduced. Short-chain and long-chain acyl-carnitines were augmented in both plasma and skeletal muscle. Oral carnitine therapy improved muscle strength.

Topics: Carnitine; Child, Preschool; Female; Glycogen; Histocytochemistry; Humans; Lactates; Lipid Metabolism; Mitochondria, Muscle; Muscles; Muscular Diseases

Topics: Adenylyl Cyclases; Adolescent; Carnitine; Carnitine O-Palmitoyltransferase; Enflurane; Glycogen; Humans; Methyl Ethers; Muscles; Muscular Diseases; Myoglobinuria; Necrosis; Syndrome

Topics: Adenosine Triphosphate; Animals; Blood Glucose; Creatine Kinase; Female; Glycogen; Hydrogen-Ion Concentration; Lactates; Male; Muscles; Muscular Diseases; Pituitary Hormones, Anterior; Stress, Physiological; Swine; Swine Diseases; Syndrome

In a muscle biopsy specimen from a baby girl with hypotonia, there was the ultrastructural finding of selective myosin degeneration in some myofibers. The sarcomeres were either well aligned or completely distorted. Excessive glycogen, fiber and fibril splitting, and occasional aggregates of vesicles were the other abnormalities present.

Topics: Female; Glycogen; Humans; Inclusion Bodies; Infant; Muscular Diseases; Myofibrils; Myosins; Sarcoplasmic Reticulum

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.

Topics: Adult; Carnitine; Carnitine O-Acetyltransferase; Carnitine O-Palmitoyltransferase; Cholesterol; Electromyography; Glycogen; Humans; Lipase; Lipid Metabolism; Male; Muscular Diseases; Palmitoyl Coenzyme A; Phospholipids; Triglycerides

A biopsy taken from the right m. gastrocnemius of a sporadic case of central core disease has been investigated by electronmicroscopy. Both longitudinal and cross sections show cores, which are partially in the centre and partially near the sarcolemma of the muscle fibres. These cores are more or less sharply delimited from the intact areas of the muscle fibres. A zone showing a severe destruction of the regularly fibrillar structure is observed in the centre of each core. This destruction zone is surrounded by a transition zone, in which a partial lesion of the fibrillar structure is found whereas the sarcomeric segmentation is preserved. The width of the interfibrillar sarcoplasm is reduced, frequently, however, mitochondria containing cristae of normal structure are observed. The cores are foundlimited by target fibres. Pathogenetically, the damages of z-lines are assumed to be dominant in the formation of the cores.

Topics: Child, Preschool; Female; Glycogen; Humans; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Myofibrils

The carbohydrate metabolism in hypothyroid patients was investigated. After an overnight fast, the blood glucose level was 24% lower and the blood lactate level was 35% lower in the untreated hypothyroid patients than that observed in the treated hypothyroid patients or in the normal subjects. There was no difference in the blood alanine or plasma free fatty acid values between the subject groups. Skeletal muscle biopsied from two hypothyroid patients with marked myopathy showed normal glycogen content, 0.83%-0.86% (normal 1.06%), but reduced activity of acid maltase, 32-50 nmoles/min/g (normal 97). Forearm ischemic stimulation applied to hypothyroid patients failed to elevate the level of lactate. The results are compatible with impaired glycogenolysis from the skeletal muscle, which may be a contributory factor in the myopathy in hypothyroidism.

Topics: Adolescent; Adult; Alanine; Blood Glucose; Creatine Kinase; Fatty Acids, Nonesterified; Female; Glycogen; Humans; Hypothyroidism; Ischemia; Lactates; Male; Middle Aged; Muscles; Muscular Diseases; Reference Values; Thyrotropin

Topics: Actinin; Animals; Glycogen; Humans; Inclusion Bodies; Muscles; Muscular Diseases; Myofibrils; Myosins; Rabbits; Sarcoplasmic Reticulum

Transvenous right ventricular endomyocardial biopsy in an 11-yr-old boy with a proximal skeletal myopathy and a cardiomyopathy, has shown a major increase in mitochondrial size and numbers on electron-microscopic morphometry, with formation of unique ring-shaped mitochondria in cardiac muscle cells. The significance of this finding and the use of cardiac biopsy in children are discussed.

Topics: Cardiomyopathies; Child; Glycogen; Humans; Male; Microtubules; Mitochondria, Muscle; Muscular Diseases; Myocardium; Myofibrils

We established muscle-tissue cultures from biopsy of a patient with adult-onset acid maltase deficiency. Morphologically and biochemically, the newly grown fibers of the cultured muscle showed the same abnormalities as those of the biopsied muscle. Light microscopy showed multiple vacuoles filled with acid-phosphatase-positive material; on ultrastructural examination there was abnormal accumulation of glycogen in membrane-bound sacs (secondary lysosomes), some of which also contained dark membranous of homogeneous material. Acid maltase (pH 4.0), a lysosomal enzyme, was undetectable in either cultured or biopsied muscle by maltose hydrolysis, whereas acid phosphatase, also a lysosomal enzyme, was increased in both sources of muscle cells. Cultured muscle fibers demonstrate the same morphologic and biochemical abnormalities characteristic of biopsied muscle, supporting the concept of a biochemically distinct primary myopathy in man.

Topics: Acid Phosphatase; Adult; Age Factors; Creatine Kinase; Culture Techniques; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Lysosomes; Male; Muscles; Muscular Diseases

In the second known case of non-thyroidal hypermetabolism (Luft's disease), there were large areas of mitochondrial aggregates in all fibers. Many mitochondria were abnormally large and contained packed cristae. In isolated mitochondrial fractions, studies of oxidative phosphorylation showed defective respiratory control and normal phosphorylation capacity ("loose coupling"). Spectra and content of cytochromes were normal. Basal ATPase activity was seven times greater than normal and poorly stimulated by 2,4-dinitrophenol. The rate of energy-dependent calcium uptake by isolated mitochondria was normal, but the amount of calcium accumulated was much decreased. Calcium could not be retained and was spontaneously released into the medium within 30 seconds. "Recycling" of calcium between mitochondria and cytosol may take place in vivo and result in sustained stimulation of respiration and loose coupling.

Topics: Adult; Calcium; Female; Glycogen; Humans; Metabolic Diseases; Mitochondria, Muscle; Muscles; Muscular Diseases; Oxidative Phosphorylation

A suspected case of xanthine oxidase deficiency has been further investigated. The patient complained of arthralgia and myalgia. Further studies included histochemical and ultramicroscopic analysis of muscle sarcoplasmic reticulum, and biochemical studies. High levels of xanthine and hypoxanthine were found, while uric acid was absent in the muscle extracts.

Topics: Adenosine Triphosphatases; Adult; Calcium; Dihydrolipoamide Dehydrogenase; Female; Glucosephosphates; Glycogen; Histocytochemistry; Humans; Hypoxanthines; Muscles; Muscular Diseases; Phosphocreatine; Sarcoplasmic Reticulum; Uric Acid; Xanthines

Histochemical, ultrastructural and biochemical studies were performed on muscle biopsy specimens from a 30-year-old man with proximal limb weakness. Modified Gomori trichome stains of anterior tibial muscle revealed accumulations of red-staining material in the subsarcolemmal and intermyofibrillar regions of virtually every fiber (ragged-red fibers); these accumulations were rich in oxidative enzymes. Electron microscopy of this muscle showed that the red-staining areas consisted of large collections of abnormal-appearing mitochondria. Mitochondria isolated from the quadriceps muscle showed lack of respiratory control with alpha-glycerophosphate as substrate. However, the lack of respiratory control with alpha-glycerophosphate must be interpreted with caution since the quadriceps muscle was severely degenerated, and biochemical alterations of mitochondria may occur secondary to muscle degeneration itself. Nevertheless, this is the second reported case of lack of respiratory control with alpha-glycerophosphate in a patient with ragged-red fibers. Further interpretation of this defect and its significance must await more studies to determine whether this muscle mitochondrial abnormality is a common finding in the disorders in which ragged-red fibers are encountered.

Topics: Adenosine Triphosphatases; Adult; Glycerophosphates; Glycogen; Histocytochemistry; Humans; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Myofibrils; Oxidative Phosphorylation; Oxygen Consumption

Pathologic findings in biopsied rectus femoris muscle underlying an area of linear scleroderma are described. The affected muscle was weak and atrophic. On electromyography it showed motor unit potentials of decreased amplitude and duration. Light microscopic changes were minimal. There was atrophy of some histochemical type I fibers. More prominent changes were found at the ultrastructural level, where many of the capillary basal laminae were thickened and reduplicated. Most striking was the presence of two types of electron-dense, rounded inclusions within the mitochondria, one ranging from 29 to 47nm in diameter and the other from 54 to 131 nm in diameter.

Topics: Action Potentials; Adult; Basement Membrane; Biopsy; Capillaries; Electromyography; Glycogen; Histocytochemistry; Humans; Inclusion Bodies; Male; Microscopy, Electron; Mitochondria, Muscle; Motor Neurons; Muscles; Muscular Diseases; Myofibrils; Scleroderma, Localized

An 11-year old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement.

Topics: Adenosine Triphosphatases; Betaine; Carnitine; Child; Endoplasmic Reticulum; Forearm; Glycogen; Histocytochemistry; Humans; Lipid Metabolism; Liver; Male; Microscopy, Electron; Mitochondria, Muscle; Mixed Function Oxygenases; Muscles; Muscular Atrophy; Muscular Diseases; NADH, NADPH Oxidoreductases; Oxidoreductases

Topics: Alcoholism; Chlorides; Chronic Disease; Creatine Kinase; Extracellular Space; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Lactates; Male; Membrane Potentials; Muscle Cramp; Muscles; Muscular Diseases; Phosphates; Phosphorus; Potassium; Sodium; Water

Topics: Diagnosis, Differential; Glucosidases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Lysosomes; Male; Middle Aged; Muscular Diseases

Topics: Adult; Glycogen; Glycogen Storage Disease; Humans; Male; Muscles; Muscular Diseases

A 34-year-old chronic alcoholic with acute alcoholic intoxication was found to have extensive aggregates on muscle biopsy performed 48 hours after admission. Forearm ischemic exercise failed to demonstrate normal generation of lactic acid. Pathologic changes in the muscle biopsy consisted of subsarcolemmal accumulations of bright purple-red material with trichrome reaction. This material stained darkly with NADH-TR but was unstained with myofibrillar ATPase and Pas. Ultrastructural studies revealed that these regions contained tubular aggregates. A second biopsy 7 days later failed to demonstrate any significant abnormalities. Two weeks later, lactate generation was normal. Previous observations by other authors that tubular aggregates may be concerned with correction of metabolic defect or detoxification of endogenous toxins could apply in our case.

Topics: Adult; Alcoholism; Biopsy; Glycogen; Histological Techniques; Humans; Kinetics; Lactates; Male; Microscopy, Electron; Muscles; Muscular Diseases; Myofibrils

The authors explored a group of patients suffering from rheumatic pelvispondylitis from the point of view of muscular lesions: clinical muscular examination, anatomo-pathological investigation of the muscle (optical microscopy, histochemistry), electromyographic investigation, and determination of certain serum and muscle enzymes. Some muscular anomalies were observed, which were predominant in the muscles of the lumbar grooves, although there were some lesions of the quadriceps muscle, with a myogenous appearance, but without inflammation. The clearest anomalies were neurogenic and were present particularly in the muscles of the lumbar grooves.

Topics: Adult; Electromyography; Glycogen; Histocytochemistry; Humans; Hyperplasia; Leg; Male; Middle Aged; Motor Activity; Muscles; Muscular Diseases; Neural Conduction; Neurologic Manifestations; Neuromuscular Diseases; Reflex, Monosynaptic; Spine; Spondylitis, Ankylosing

Thick round fibres common in cross sections of muscle biopsies from patients with muscular dystrophy are due to contracted and swollen segments of otherwise normal muscle fibres. This contracture leads to segmental fibre breakdown, which is identical with Zenker's waxy degeneration. In biopsies from 90 patients suspected of neuromuscular disease, segmental contracture was seen in all or nearly all patients with infantile muscular dystrophy, necrotic myopathy or acute alcoholic myopathy. It was present in half of the patients with polymyositis or myotonic dystrophy. In resticted forms of muscular dystrophy it was rare as it was in neurogenic atrophy. In 9 clinically normal patients it was absent. In electron micrographs of the initial stage sarcomeres were moderately shortened, the sarcoplasmic reticulum was distended and the mitochondria were normal. In the plasmalemma holes were found, through which glycogen granules were lost into the interstitial tissue. In later stages myofibrils were overcontracted and homogenized; in large areas the plasmalemma was absent. Based on these findings a hypothesis for the development of waxy degeneration is proposed: locally defects of the plasmamembrane cause segmental contracture, glycogen granules and water soluble enzymes are lost through holes in the plasma membrane, and finally the affected fibre segment becomes necrotic.

Topics: Adolescent; Adult; Aged; Basement Membrane; Child; Child, Preschool; Female; Glycogen; Humans; Infant; Male; Middle Aged; Mitochondria, Muscle; Muscle Contraction; Muscles; Muscular Diseases; Muscular Dystrophies; Myofibrils; Myotonic Dystrophy; Neuromuscular Diseases; Sarcolemma; Sarcoplasmic Reticulum

We have presented evidence that in an in vitro system, glycogenolysis and glycolysis function normally at potassium levels far below those observed in muscle cell water of severely deficient dogs. We suggest that a functional impairment of glycogenolysis or glycolysis is unlikely to be a mechanism by which potassium deficiency leads to rhabdomyolysis.

Topics: Animals; Dogs; Energy Metabolism; Glycogen; Glycolysis; Lactates; Muscles; Muscular Diseases; Physical Exertion; Potassium; Potassium Deficiency

Topics: Acetone; Actomyosin; Adenosine Triphosphatases; Animals; Creatine Kinase; Fructosephosphates; Glucose; Glucosephosphates; Glycogen; Glycogen Synthase; Glycolysis; In Vitro Techniques; Lactates; Male; Muscle Proteins; Muscles; Muscular Diseases; Rabbits; Time Factors; Triamcinolone

Topics: Biopsy; Body Weight; Cardiomyopathies; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Infant, Newborn; Liver; Muscles; Muscular Diseases; Prenatal Diagnosis; Skin

Topics: Acid Phosphatase; Adenosine Triphosphatases; Chronic Disease; Creatine Kinase; Female; Glycogen; Histocytochemistry; Humans; Inclusion Bodies; Lipid Metabolism; Lipoproteins; Microscopy, Electron; Middle Aged; Muscles; Muscular Diseases; Myofibrils; NAD; Succinate Dehydrogenase

Topics: Animals; Electron Transport Complex IV; Glycogen; L-Lactate Dehydrogenase; Male; Microscopy, Electron; Muscles; Muscular Diseases; Rats; Succinate Dehydrogenase; Time Factors; Wounds and Injuries

Topics: Adolescent; Adrenal Cortex Hormones; Basement Membrane; Biopsy; Capillaries; Child; Child, Preschool; Creatine; Electromyography; Female; Glycogen; Histocytochemistry; Humans; Male; Microscopy, Electron; Muscles; Muscular Diseases; Prednisone; Sarcoplasmic Reticulum

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Creatine Kinase; Fructose-Bisphosphate Aldolase; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Humans; Ischemia; Lactates; Male; Muscles; Muscular Diseases; Phosphorylase Kinase; Physical Exertion; Pyruvates; Syndrome

Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Blood Proteins; Electric Stimulation; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Lactates; Lipid Metabolism; Male; Muscles; Muscular Diseases; Pyruvates; Seizures; Syndrome

Topics: Biopsy; Cell Nucleus; Child; Female; Glycogen; Golgi Apparatus; Histocytochemistry; Humans; In Vitro Techniques; Lipids; Methods; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Muscular Dystrophies; Myofibrils; Regeneration; Sarcolemma; Sarcoplasmic Reticulum

Topics: Action Potentials; Child; Child, Preschool; Congenital Hypothyroidism; Creatine Kinase; Electromyography; Female; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Hypertrophy; Hypothyroidism; L-Lactate Dehydrogenase; Lipid Metabolism; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Neuromuscular Junction; Sarcoplasmic Reticulum; Syndrome; Thyroxine

Topics: Cells, Cultured; Culture Media; DNA; Fibroblasts; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Synthase; Glycoside Hydrolases; Heart Diseases; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Liver Diseases; Methods; Muscular Diseases; Phosphorylases; Proteins

Topics: Age Factors; Alanine Transaminase; Aspartate Aminotransferases; Carbohydrate Epimerases; Carbohydrate Metabolism, Inborn Errors; Creatine Kinase; Female; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Infant; L-Lactate Dehydrogenase; Lipid Metabolism, Inborn Errors; Mitochondria, Muscle; Muscular Diseases; Phosphofructokinase-1; Phosphoglucomutase; Phosphorylase Kinase; Pyruvate Kinase

Topics: Adenosine Triphosphatases; Adolescent; Biopsy; Glycerolphosphate Dehydrogenase; Glycogen; Histocytochemistry; Humans; Male; Marfan Syndrome; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Myofibrils; NAD; Sarcolemma; Sarcoplasmic Reticulum

Topics: Adult; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Male; Muscles; Muscular Diseases; Phosphoenolpyruvate; Phosphotransferases

Topics: Adolescent; Blood Glucose; Electrophoresis, Polyacrylamide Gel; Forearm; Glucose Tolerance Test; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Iodine; Lactates; Liver Diseases; Magnetic Resonance Spectroscopy; Male; Microscopy, Electron; Muscle Proteins; Muscles; Muscular Diseases; Physical Exertion; Spectrophotometry, Infrared

Topics: Animals; Blood Glucose; Blood Urea Nitrogen; Cattle; Cattle Diseases; Creatine Kinase; Epinephrine; Fasting; Female; Glycogen; Humans; Hydrogen-Ion Concentration; Hypertrophy; Lactates; Muscles; Muscular Diseases; Physical Exertion; Stress, Physiological; Stress, Psychological

Topics: Age Factors; Aspartate Aminotransferases; Biopsy; Creatine Kinase; Female; Glycogen; Humans; Infant; L-Lactate Dehydrogenase; Lipid Metabolism; Mitochondria, Muscle; Muscles; Muscular Diseases

Topics: Animals; Basement Membrane; Blood Vessels; Glycogen; Histocytochemistry; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Microscopy, Electron; Mitochondria; Muscles; Muscular Diseases; Myofibrils; Nerve Endings

Topics: Acid Phosphatase; Biopsy; Child; Glucosidases; Glucosyltransferases; Glucuronidase; Glycogen; Glycogen Storage Disease; Hexosaminidases; Histocytochemistry; Humans; Intellectual Disability; Male; Microscopy; Microscopy, Electron; Muscles; Muscular Atrophy; Muscular Diseases

Topics: Adipose Tissue; Age Factors; Aged; Basement Membrane; Biopsy; Cell Nucleus; Cytoplasmic Granules; Endothelium; Female; Glycogen; Humans; Hypertrophy; Lysosomes; Microscopy, Electron; Mitochondria; Muscles; Muscular Diseases; Myofibrils; Nerve Endings; Neuromuscular Junction; Sarcolemma; Staining and Labeling

Topics: Acute Kidney Injury; Adolescent; Adult; Biopsy; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Hypercalcemia; Male; Muscles; Muscular Diseases; Myoglobinuria; Nucleoside Diphosphate Sugars

Topics: Action Potentials; Animals; Electromyography; Female; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycolates; Histocytochemistry; Hydrocarbons, Halogenated; Muscle Contraction; Muscle Tonus; Muscles; Muscular Diseases; Myofibrils; Phosphorylases; Rats; Rats, Inbred Strains

Topics: Adult; Age Factors; Cell Membrane; Cells, Cultured; Cytoplasm; Fascia; Fibroblasts; Glucosidases; Glycogen; Glycogen Storage Disease; Heart Diseases; Histocytochemistry; Humans; Hydrogen-Ion Concentration; Maltose; Microscopy, Electron; Middle Aged; Muscular Diseases; Skin

Topics: Biopsy; Glycogen; Histocytochemistry; Histological Techniques; Humans; Methods; Microscopy, Electron; Muscle Denervation; Muscles; Muscular Atrophy; Muscular Diseases; Paraffin

Repeated administration of ethanol (42 percent of total calories) for 28 days increased serum creatine phosphokinase activity and produced ultrastructural changes in skeletal muscle of human volunteers. The data suggest that alcoholic myopathy results from ethanol toxicity, rather than from nutritional or other factors.

Topics: Adult; Biopsy; Creatine Kinase; Diet; Ethanol; Glycogen; Humans; Lipids; Male; Microscopy; Microscopy, Electron; Mitochondria; Muscles; Muscular Diseases; Sarcoplasmic Reticulum

Topics: Adolescent; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Dwarfism; Female; Glycogen; Humans; Hypogonadism; Infant; Intellectual Disability; Male; Microcephaly; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Xeroderma Pigmentosum

Topics: Animals; Chick Embryo; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Methods; Microscopy, Electron; Muscles; Muscular Diseases; Osmium; Silver; Staining and Labeling; Uranium

Topics: Biopsy; Cardiomegaly; Diagnosis, Differential; Glucose-6-Phosphatase; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Heart Defects, Congenital; Heart Diseases; Humans; Infant; Liver; Male; Methods; Muscles; Muscular Diseases; Skin

Topics: Adult; Electromyography; Glycogen; Humans; Male; Muscular Diseases

Topics: Basement Membrane; Biopsy; Cell Nucleus; Child, Preschool; Cytoplasm; Extracellular Space; Female; Glycogen; Humans; Intellectual Disability; Microscopy, Electron; Muscles; Muscular Diseases; Myofibrils; Neuromuscular Diseases; Pinocytosis; Reflex, Abnormal; Sarcolemma; Thigh

Topics: Animals; DNA; Environmental Exposure; Glycogen; Muscle Proteins; Muscles; Muscular Diseases; Nucleic Acids; Occupational Medicine; Rats; RNA; Rupture; Ultrasonics; Vibration

Topics: Child, Preschool; Congenital Hypothyroidism; Glycogen; Histocytochemistry; Humans; Hypertrophy; Hypothyroidism; Male; Muscles; Muscular Diseases

Topics: Adult; Alcoholism; Aspartate Aminotransferases; Chronic Disease; Creatine Kinase; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Hypokalemia; Male; Middle Aged; Muscles; Muscular Diseases; Necrosis; Potassium; Sodium

Topics: Acetates; Animals; Cell Nucleus; Chick Embryo; Cytoplasm; Glycogen; Humans; Methods; Mice; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Myocardium; Myofibrils; Staining and Labeling; Uranium

Topics: Adolescent; Amyotrophic Lateral Sclerosis; Animals; Biopsy; Cats; Dermatomyositis; Esterases; Female; Glucosyltransferases; Glycogen; Guinea Pigs; Histocytochemistry; Humans; Male; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Myofibrils; Nervous System Diseases; Oxidoreductases; Paralysis; Rabbits; Schwann Cells; Staining and Labeling; Transferases; Tyrosine

Topics: Adult; Biopsy; Diagnosis, Differential; Female; Glucose; Glucosidases; Glycogen; Glycogen Storage Disease; Golgi Apparatus; Histocytochemistry; Humans; In Vitro Techniques; Lactates; Male; Metabolism, Inborn Errors; Microscopy, Electron; Microscopy, Phase-Contrast; Middle Aged; Mitochondria, Muscle; Muscles; Muscular Diseases; Muscular Dystrophies

Topics: Autopsy; Biopsy; Cardiomyopathies; Glucosidases; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Humans; Infant; Kidney; Kidney Diseases; Liver; Liver Diseases; Microscopy, Electron; Muscles; Muscular Diseases; Myocardium; Ultracentrifugation

Topics: Adult; Basement Membrane; Biopsy; Chlorides; Diabetes Complications; Diabetes Mellitus; Edema; Glycogen; Humans; Magnesium; Methods; Microscopy, Electron; Middle Aged; Muscle Proteins; Muscles; Muscular Atrophy; Muscular Diseases; Phosphorus; Potassium; Sodium

Topics: Adult; Child; Child, Preschool; Consanguinity; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Infant; Liver Diseases; Liver Glycogen; Male; Muscular Diseases; Pedigree

Topics: Carbon Isotopes; Glucose; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycoside Hydrolases; Hepatitis; Humans; Jaundice, Chronic Idiopathic; Liver Diseases; Liver Glycogen; Molecular Weight; Muscular Diseases; Phosphorylases; Ultracentrifugation

Topics: Adolescent; Adrenal Glands; Calcitonin; Carcinoma; Eyelid Neoplasms; Female; Glycogen; Histocytochemistry; Humans; Marfan Syndrome; Melanosis; Microscopy, Electron; Mucous Membrane; Muscles; Muscular Diseases; Neoplasms, Multiple Primary; Neuroma; Pituitary-Adrenal Function Tests; Thyroid Function Tests; Thyroid Gland; Thyroid Neoplasms; Tongue; Tongue Neoplasms

Topics: Adolescent; Biopsy; Child; Child, Preschool; Glucosyltransferases; Glycogen; Humans; Hydrolases; Muscular Diseases; Muscular Dystrophies

Topics: Aged; Biopsy; Cataract; Diabetes Complications; Diabetes Mellitus; Dupuytren Contracture; Electromyography; Female; Glycogen; Humans; Lactates; Male; Middle Aged; Muscles; Muscular Diseases; Physical Exertion; Transferases

Topics: Acetates; Action Potentials; Animals; Buttocks; Calcium Phosphates; Cell Nucleolus; Cell Nucleus; Chromatin; Cytoplasm; Fats; Glycogen; Golgi Apparatus; Humans; Hydrocortisone; Infant; Injections, Intramuscular; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Diseases; Myofibrils; Rabbits; Triamcinolone

Topics: Animals; Autoradiography; Basophils; Endoplasmic Reticulum; Fluorescent Antibody Technique; Glycogen; Histocytochemistry; Humans; Muscles; Muscular Diseases; Phosphoric Monoester Hydrolases; Trichinellosis

Topics: Adult; Blood Glucose; Diagnosis, Differential; Electromyography; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Lactates; Male; Microscopy, Electron; Muscles; Muscular Diseases; Phosphorylase Kinase; Physical Exertion

Topics: Acclimatization; Alanine Transaminase; Animals; Blood Glucose; Cold Temperature; Corticosterone; Glycerolphosphate Dehydrogenase; Glycogen; L-Lactate Dehydrogenase; Liver; Malate Dehydrogenase; Male; Muscular Diseases; Necrosis; Physical Exertion; Rats

Topics: Adult; Aged; Antibodies; Child; Culture Techniques; Dermatomyositis; Female; Glycogen; Humans; Lymphocyte Activation; Lymphocytes; Male; Metabolic Diseases; Middle Aged; Muscles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies

Topics: Adolescent; Adult; Cell Nucleus; Child, Preschool; Endoplasmic Reticulum; Female; Glycogen; Humans; Male; Microscopy, Electron; Mitochondria; Muscular Diseases; Muscular Dystrophies

Topics: Glycogen; Humans; Microscopy, Electron; Muscular Diseases; Myotonic Dystrophy; Staining and Labeling

Topics: Action Potentials; Child, Preschool; Electromyography; Epinephrine; Glucosidases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Male; Muscle Contraction; Muscles; Muscular Diseases; Urinary Bladder

Topics: Adult; Deficiency Diseases; Diagnosis, Differential; Electrocardiography; Electromyography; Female; Glucose Tolerance Test; Glycogen; Glycogen Storage Disease; Glycoside Hydrolases; Humans; Injections, Intravenous; Microscopy, Electron; Muscles; Muscular Diseases; Muscular Dystrophies; Time Factors

Topics: Child; Female; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Liver; Liver Diseases; Muscles; Muscular Diseases

Topics: Adult; Aged; Carbohydrate Metabolism; Diabetes Complications; Diabetic Neuropathies; Electromyography; Female; Glycogen; Humans; Male; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Muscular Diseases; Vision Disorders

Topics: Carcinoma, Squamous Cell; Glycogen; Glycolipids; Glycoproteins; Histocytochemistry; Humans; Methods; Muscular Diseases; Myasthenia Gravis; Organ Size; Oxidoreductases; Radiation Effects; RNA; Thymoma; Thymus Gland; Thymus Hyperplasia; Thymus Neoplasms

Topics: Adolescent; Carbohydrate Metabolism, Inborn Errors; Diagnosis, Differential; Glycogen; Humans; Intermittent Claudication; Male; Muscular Diseases

Topics: Adult; Carbohydrate Metabolism, Inborn Errors; Female; Glycogen; Humans; Male; Muscular Diseases

Topics: Adolescent; Adult; Carbohydrate Metabolism, Inborn Errors; Child; Glucosyltransferases; Glycogen; Histocytochemistry; Humans; Male; Muscles; Muscular Diseases; Myofibrils

Topics: Child; Child, Preschool; Citrates; Diagnosis, Differential; Female; Glycogen; Humans; Lactates; Male; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Poliomyelitis; Pyruvates

Topics: Adolescent; Diagnosis, Differential; Fatty Acids; Glycogen; Glycogen Storage Disease; Glycolysis; Humans; Male; Metabolism, Inborn Errors; Muscular Diseases; Pedigree; Phosphofructokinase-1; Phosphorus Metabolism Disorders

Topics: Adult; Biopsy; Child; Clinical Enzyme Tests; Diagnosis, Differential; Enzyme Repression; Female; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Humans; Isomerases; Microscopy, Electron; Mitochondria, Muscle; Muscular Diseases; Muscular Dystrophies; Phosphofructokinase-1

Topics: Glycogen; Humans; Hypokalemia; Muscle Spindles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Myofibrils; Myositis; Paralysis; Polymyalgia Rheumatica

Topics: Carbohydrates; Child; Glucosidases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Life Expectancy; Liver; Lysosomes; Male; Microscopy, Electron; Muscles; Muscular Diseases; Myocardium; Polysaccharides

Topics: Adult; Electric Stimulation; Electromyography; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Ischemia; Lactates; Male; Microscopy, Electron; Muscle Contraction; Muscles; Muscular Diseases; Myofibrils; Neural Conduction; Pyruvates

Topics: Blepharoptosis; Female; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Humans; Infant; Leukocytes; Liver; Muscles; Muscular Diseases; Respiratory Insufficiency

Topics: Adult; Enzymes; Glycogen; Glycogen Storage Disease; Humans; Male; Muscle Contraction; Muscular Diseases

Topics: Acid Phosphatase; Cholinesterases; Glucosephosphate Dehydrogenase; Glycerolphosphate Dehydrogenase; Glycogen; Humans; L-Lactate Dehydrogenase; Malate Dehydrogenase; Methods; Muscles; Muscular Diseases; Myofibrils; Oxidoreductases; Oxygen; Succinate Dehydrogenase; Water-Electrolyte Balance

Topics: Adolescent; Child; Child, Preschool; Femur Neck; Glucosyltransferases; Glycogen; Hip Dislocation, Congenital; Humans; Methods; Muscles; Muscular Diseases; Poliomyelitis

Topics: Animals; Diabetes Mellitus; Dogs; Enzymes; Glycogen; Histocytochemistry; Microscopy, Electron; Muscular Diseases; Neoplasms, Experimental; Rabbits

Topics: Aniline Compounds; Animals; Electron Transport Complex IV; Glucosyltransferases; Glycogen; Histocytochemistry; In Vitro Techniques; Lipid Metabolism; Mice; Microscopy, Electron; Muscle Denervation; Muscles; Muscular Diseases; Succinate Dehydrogenase

Topics: Glycogen; Glycolysis; Histocytochemistry; Humans; In Vitro Techniques; Mitochondria; Muscle Contraction; Muscular Diseases; Myofibrils; Proteins

Topics: Animals; Cortisone; Female; Glycogen; Lipid Metabolism; Microscopy, Electron; Mitochondria; Muscular Diseases; Myofibrils; Photomicrography; Rabbits

Topics: Adolescent; Blood Chemical Analysis; Electromyography; Glycogen; Glycogen Storage Disease Type V; Histocytochemistry; Humans; Muscles; Muscular Diseases; Myoglobinuria; Necrosis; Pathology; Phosphotransferases; Physical Exertion; Regeneration; Rhabdomyolysis; Seizures

Topics: Adolescent; Biochemical Phenomena; Biochemistry; Blood; Carbohydrate Metabolism; Citric Acid Cycle; Enzymes; Glucose Tolerance Test; Glycogen; Hemoglobins; Humans; Lactates; Muscles; Muscular Diseases; Myoglobinuria; Phosphates; Pyruvates

Topics: Adult; Carbohydrate Metabolism, Inborn Errors; Glycogen; Humans; Muscular Diseases

Topics: Adolescent; Adult; Aged; Child; Dermatomyositis; Glycogen; Glycolysis; Hexosephosphates; Humans; Lactates; Middle Aged; Motor Neurons; Muscles; Muscular Diseases; Muscular Dystrophies; Myasthenia Gravis; Myositis; Oculomotor Muscles; Phosphotransferases; Polyarteritis Nodosa

Topics: Adenine Nucleotides; Adenosine Triphosphate; Blood Chemical Analysis; Contracture; Electromyography; Glycogen; Humans; In Vitro Techniques; Lactates; Metabolism, Inborn Errors; Muscle Contraction; Muscle Cramp; Muscle Proteins; Muscles; Muscular Diseases; Myoglobinuria; Phosphocreatine; Phosphotransferases; Physical Exertion; Spectrophotometry

Topics: Adrenocorticotropic Hormone; Biopsy; Blood Chemical Analysis; Extremities; Glucose; Glycogen; Glycogen Storage Disease; Glycosaminoglycans; Humans; Insulin; Lactates; Muscles; Muscular Diseases; Physical Exertion; Prednisolone; Pyruvates; Rest; Twins

Topics: Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Hyperplasia; Hypertrophy; Infant; Liver Diseases; Metabolic Diseases; Metabolism; Muscular Diseases

Topics: Blood; Child; Electromyography; Epinephrine; Fructose; Genetics, Medical; Glucose; Glycogen; Glycogen Storage Disease Type V; Histocytochemistry; Humans; Lactates; Muscular Diseases; Pain; Pathology; Phosphotransferases; Physical Exertion; Pyruvates

Topics: Animals; Coenzymes; Creatine; Creatinine; Glutathione; Glycogen; Histocytochemistry; Leg; Metabolism; Mice; Muscle, Skeletal; Muscular Diseases; Pathology; Peptides; Phosphocreatine; Sarcocystosis

Topics: Blood; Blood Chemical Analysis; Carbohydrate Metabolism; Clinical Enzyme Tests; Diagnosis, Differential; Dietary Carbohydrates; Electromyography; Glucose Tolerance Test; Glycogen; Humans; Lactates; Metabolism; Muscles; Muscular Diseases; Myoglobinuria; Physical Exertion; Spirometry; Urine

Topics: Amyloidosis; Carbohydrate Metabolism; Congenital Abnormalities; Endocrinology; Glycogen; Humans; Mitochondria; Muscular Diseases; Muscular Dystrophies; Myositis; Neurology; Neuromuscular Diseases; Paralyses, Familial Periodic

Topics: Adenine Nucleotides; Adenosine Triphosphate; Adolescent; Blood Chemical Analysis; Child; Coenzymes; Creatine; Creatinine; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Pathology; Phosphates

Topics: Carbohydrate Metabolism; Disease; Glucose; Glycogen; Humans; Intestinal Absorption; Intestines; Muscles; Muscular Diseases

Topics: Disease; Glycogen; Glycogenolysis; Hemoglobinuria; Humans; Muscles; Muscular Diseases; Myoglobinuria

Topics: Animals; Disease; Glycogen; Glycogen Phosphorylase, Muscle Form; Mice; Muscle, Skeletal; Muscles; Muscular Diseases; Phosphorylases

Topics: Disease; Glycogen; Glycogen Storage Disease; Humans; Muscle, Skeletal; Muscles; Muscular Diseases

Topics: Disease; Glycogen; Glycogen Storage Disease; Humans; Liver; Muscle, Skeletal; Muscles; Muscular Diseases

Topics: Disease; Glycogen; Glycogen Storage Disease; Humans; Muscle, Skeletal; Muscles; Muscular Diseases; Neuromuscular Diseases

Topics: Glycogen; Glycogenolysis; Humans; Muscles; Muscular Diseases