glycogen and Muscle-Cramp

The syndrome of exercise intolerance, cramps, and myoglobinuria is a common presentation of metabolic myopathies and has been associated with several specific inborn errors of glycogen or lipid metabolism. As disorders in fuel utilization presumably impair muscle energy production, it was more than a little surprising that exercise intolerance and myoglobinuria had not been associated with defects in the mitochondrial respiratory chain, the terminal energy-yielding pathway. Recently, however, specific defects in complex I, complex III, and complex IV have been identified in patients with severe exercise intolerance with or without myoglobinuria. All patients were sporadic cases and all harbored mutations in protein-coding genes of muscle mtDNA, suggesting that these were somatic mutations not affecting the germ-line. Another respiratory chain defect, primary coenzyme Q10 (CoQ10) deficiency, also causes exercise intolerance and recurrent myoglobinuria, usually in conjunction with brain symptoms, such as seizures or cerebellar ataxia. Primary CoQ10 deficiency is probably due to mutations in nuclear gene(s) encoding enzymes involved in CoQ10 biosynthesis.

Topics: Adolescent; Adult; Coenzymes; Electron Transport; Electron Transport Complex I; Electron Transport Complex III; Energy Metabolism; Exercise; Exercise Tolerance; Fatty Acids; Female; Glycogen; Humans; Intracellular Membranes; Male; Metabolism, Inborn Errors; Middle Aged; Mitochondria, Muscle; Mitochondrial Myopathies; Muscle Cramp; Muscles; Myoglobinuria; NADH, NADPH Oxidoreductases; Ubiquinone

Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both.

Topics: Adult; Creatine Kinase; Glycogen; Humans; Male; Middle Aged; Muscle Cramp; Muscle Proteins; Muscles; Muscular Atrophy; Phosphorylase Kinase; Physical Exertion; Syndrome; X Chromosome

We report here findings in a 51-year-old Japanese man with non-insulin-dependent diabetes mellitus who complained of exercise-induced cramps. Muscle biopsy showed scattered regenerating fibers, small angular fibers and increased PAS positive particles. Electron microscopic examination revealed an abnormal accumulation of glycogen particles in subsarcolenmmal areas and between myofibrils while chemical studies showed an increased glycogen concentration and decreased phosphoglycerate mutase (PGAM), 46.9% of the normal mean value. Thus, partial PGAM deficiency, insulin resistance and mild diabetic sensory-motor polyneuropathy can induce severe cramps.

Topics: Biopsy; Chromosomes, Human, Pair 7; Diabetic Neuropathies; Exercise Test; Glycogen; Humans; Japan; Male; Middle Aged; Muscle Cramp; Muscle, Skeletal; Myofibrils; Phosphoglycerate Mutase; Point Mutation; Tomography, X-Ray Computed

In a number of individual cycling tests lasting 2.5-5 h with alternating exercise intensities of 50%-85% of maximal working capacity, it was observed that plasma ammonia levels may rise above 250 mumol/l when reaching exhaustion, while lactate levels remain relatively low. Acute quantitative ammonia production during intensive endurance exercise may be enhanced by a reduced glycogen availability in muscle. However, adequate amounts of glycogen itself do not prevent ammonia production when exercise is at high intensity and long-lasting. The continuous ammonia accumulation in blood during endurance exercise in trained individuals may be the result of a relatively low blood flow to the liver and thereby low clearance in contrast to lactate which may not accumulate due to a high clearance rate in both active and nonactive oxidative muscle fibers. In a number of subjects it was observed that exhaustion, when performing endurance exercise at high exercise intensities, occurred when plasma ammonia levels were high. Muscle cramps occurred in subjects who reached their highest individual ammonia values and seemed not to be related to serum potassium, plasma lactate, or muscle glycogen. These individual observations give rise to the hypothesis that high intramuscular ammonia levels may be related to the etiology of muscle exhaustion and muscle cramping during highly intensive endurance exercise.

Topics: Ammonia; Energy Metabolism; Exercise; Exercise Test; Glycogen; Humans; Muscle Contraction; Muscle Cramp; Muscles

Topics: Adenosine Triphosphate; Animals; Disease Models, Animal; Fructosediphosphates; Glycogen; Glycolysis; Hexosediphosphates; Lactates; Lactic Acid; Male; Muscle Contraction; Muscle Cramp; Muscles; Myoglobinuria; Phosphocreatine; Physical Exertion; Rats; Rats, Inbred Strains

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: Antithyroid Agents; Creatine Kinase; Fructose; Glucose; Glycogen; Humans; Hyperthyroidism; In Vitro Techniques; Ischemia; Lactates; Male; Middle Aged; Muscle Cramp; Muscles; Propylthiouracil

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: Child; Glycogen; Glycogenolysis; Humans; Infant; Muscle Cramp