Genes and exercise intolerance: insights from McArdle disease

2016 ◽  
Vol 48 (2) ◽  
pp. 93-100 ◽  
Author(s):  
Gisela Nogales-Gadea ◽  
Richard Godfrey ◽  
Alfredo Santalla ◽  
Jaume Coll-Cantí ◽  
Guillem Pintos-Morell ◽  
...  
Keyword(s):  
Glycogen Storage Disease Type ◽  
Tissue Level ◽  
Glycogen Storage ◽  
Clinical Severity ◽  
Exercise Intolerance ◽  
Moderate Intensity ◽  
Future Research ◽  
Moderate Intensity Exercise ◽  
Carbohydrate Ingestion ◽  
Mcardle Disease

McArdle disease (glycogen storage disease type V) is caused by inherited deficiency of a key enzyme in muscle metabolism, the skeletal muscle-specific isoform of glycogen phosphorylase, “myophosphorylase,” which is encoded by the PYGM gene. Here we review the main pathophysiological, genotypic, and phenotypic features of McArdle disease and their interactions. To date, moderate-intensity exercise (together with pre-exercise carbohydrate ingestion) is the only treatment option that has proven useful for these patients. Furthermore, regular physical activity attenuates the clinical severity of McArdle disease. This is quite remarkable for a monogenic disorder that consistently leads to the same metabolic defect at the muscle tissue level, that is, complete inability to use muscle glycogen stores. Further knowledge of this disorder would help patients and enhance understanding of exercise metabolism as well as exercise genomics. Indeed, McArdle disease is a paradigm of human exercise intolerance and PYGM genotyping should be included in the genetic analyses that might be applied in the coming personalized exercise medicine as well as in future research on genetics and exercise-related phenotypes.

scholarly journals McArdle Disease: New Insights into Its Underlying Molecular Mechanisms

2019 ◽  
Vol 20 (23) ◽  
pp. 5919
Author(s):  
Llavero ◽  
Arrazola Sastre ◽  
Luque Montoro ◽  
Gálvez ◽  
Lacerda ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Phosphorylase ◽  
Molecular Mechanisms ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
High Serum ◽  
Creatine Kinase Activity ◽  
Exercise Intolerance ◽  
Mcardle Disease ◽  
Type V

McArdle disease, also known as glycogen storage disease type V (GSDV), is characterized by exercise intolerance, the second wind phenomenon, and high serum creatine kinase activity. Here, we recapitulate PYGM mutations in the population responsible for this disease. Traditionally, McArdle disease has been considered a metabolic myopathy caused by the lack of expression of the muscle isoform of the glycogen phosphorylase (PYGM). However, recent findings challenge this view, since it has been shown that PYGM is present in other tissues than the skeletal muscle. We review the latest studies about the molecular mechanism involved in glycogen phosphorylase activity regulation. Further, we summarize the expression and functional significance of PYGM in other tissues than skeletal muscle both in health and McArdle disease. Furthermore, we examine the different animal models that have served as the knowledge base for better understanding of McArdle disease. Finally, we give an overview of the latest state-of-the-art clinical trials currently being carried out and present an updated view of the current therapies.

Substrate metabolism when subjects are fed carbohydrate during exercise

1999 ◽  
Vol 276 (5) ◽  
pp. E828-E835 ◽  
Author(s):  
Jeffrey F. Horowitz ◽  
Ricardo Mora-Rodriguez ◽  
Lauri O. Byerley ◽  
Edward F. Coyle
Keyword(s):  
Plasma Insulin ◽  
Fat Oxidation ◽  
Insulin Concentration ◽  
Peak Oxygen Consumption ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Plasma Insulin Concentration ◽  
Carbohydrate Ingestion ◽  
Low Intensity ◽  
Low Intensity Exercise

This study determined the effect of carbohydrate ingestion during exercise on the lipolytic rate, glucose disappearance from plasma (Rd Glc), and fat oxidation. Six moderately trained men cycled for 2 h on four separate occasions. During two trials, they were fed a high-glycemic carbohydrate meal during exercise at 30 min (0.8 g/kg), 60 min (0.4 g/kg), and 90 min (0.4 g/kg); once during low-intensity exercise [25% peak oxygen consumption (V˙o 2 peak)] and once during moderate-intensity exercise (68%V˙o 2 peak). During two additional trials, the subjects remained fasted (12–14 h) throughout exercise at each intensity. After 55 min of low-intensity exercise in fed subjects, hyperglycemia (30% increase) and a threefold elevation in plasma insulin concentration ( P < 0.05) were associated with a 22% suppression of lipolysis compared with when subjects were fasted (5.2 ± 0.5 vs. 6.7 ± 1.2 μmol ⋅ kg−1 ⋅ min−1, P < 0.05), but fat oxidation was not different from fasted levels at this time. Fat oxidation when subjects were fed carbohydrate was not reduced below fasting levels until 80–90 min of exercise, and lipolysis was in excess of fat oxidation at this time. The reduction in fat oxidation corresponded in time with the increase in Rd Glc. During moderate-intensity exercise, the very small elevation in plasma insulin concentration (∼3 μU/ml; P < 0.05) during the second hour of exercise when subjects were fed vs. when they were fasted slightly attenuated lipolysis ( P < 0.05) but did not increase Rd Glc or suppress fat oxidation. These findings indicate that despite a suppression of lipolysis after carbohydrate ingestion during exercise, the lipolytic rate remained in excess and thus did not limit fat oxidation. Under these conditions, a reduction in fat oxidation was associated in time with an increase in glucose uptake.

Confirming a beneficial effect of the six-minute walk test on exercise confidence in patients with heart failure

2019 ◽  
Vol 19 (2) ◽  
pp. 165-171 ◽  
Author(s):  
SR Toukhsati ◽  
S Mathews ◽  
A Sheed ◽  
I Freijah ◽  
L Moncur ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mixed Model ◽  
Moderate Intensity ◽  
Future Research ◽  
Walk Test ◽  
Clinical Tool ◽  
Moderate Intensity Exercise ◽  
Heart Failure Patients ◽  
Six Minute Walk Test ◽  
Minute Walk

Background: Low confidence to exercise is a barrier to engaging in exercise in heart failure patients. Participating in low to moderate intensity exercise, such as the six-minute walk test, may increase exercise confidence. Aim: To compare the effects of a six-minute walk test with an educational control condition on exercise confidence in heart failure patients. Methods: This was a prospective, quasi-experimental design whereby consecutive adult patients attending an out-patient heart failure clinic completed the Exercise Confidence Scale prior to and following involvement in the six-minute walk test or an educational control condition. Results: Using a matched pairs, mixed model design ( n=60; 87% male; Mage=58.87±13.16), we identified a significantly greater improvement in Total exercise confidence ( F(1,54)=4.63, p=0.036, partial η2=0.079) and Running confidence ( F(1,57)=4.21, p=0. 045, partial η2=0.069) following the six-minute walk test compared to the educational control condition. These benefits were also observed after adjustment for age, gender, functional class and depression. Conclusion: Heart failure patients who completed a six-minute walk test reported greater improvement in exercise confidence than those who read an educational booklet for 10 min. The findings suggest that the six-minute walk test may be used as a clinical tool to improve exercise confidence. Future research should test these results under randomized conditions and examine whether improvements in exercise confidence translate to greater engagement in exercise behavior.

Glycogen storage disease type 5, McArdle disease

2013 ◽  
pp. 150-152
Author(s):  
John H. J. Wokke ◽  
Pieter A. van Doorn ◽  
Jessica E. Hoogendijk ◽  
Marianne de Visser
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Mcardle Disease

scholarly journals From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease

2014 ◽  
Vol 72 (7) ◽  
pp. 538-541 ◽  
Author(s):  
Renata Siciliani Scalco ◽  
Sherryl Chatfield ◽  
Richard Godfrey ◽  
Jatin Pattni ◽  
Charlotte Ellerton ◽  
...  
Keyword(s):  
Signs And Symptoms ◽  
Glycogen Storage ◽  
Exercise Intolerance ◽  
Functional Improvement ◽  
Walk Test ◽  
Storage Diseases ◽  
Mcardle Disease ◽  
Glycogen Storage Diseases ◽  
Growing Pains ◽  
Minute Walk

McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to ‘growing pains’ and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.

Exercise intolerance in Glycogen Storage Disease Type III: Weakness or energy deficiency?

2013 ◽  
Vol 109 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Nicolai Preisler ◽  
Agnès Pradel ◽  
Edith Husu ◽  
Karen Lindhardt Madsen ◽  
Marie-Hélène Becquemin ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Exercise Intolerance ◽  
Energy Deficiency ◽  
Type Iii

scholarly journals Whole Exome Sequencing detects PYGM variants in two adults with McArdle disease

2022 ◽  
pp. mcs.a006173
Author(s):  
Amanda Thomas-Wilson ◽  
Avinash V Dharmadhikari ◽  
Jonas J Heymann ◽  
Vaidehi Jobanputra ◽  
Salvatore DiMauro ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Storage Disease ◽  
Missense Variant ◽  
Glycogen Storage ◽  
Exercise Intolerance ◽  
Mcardle Disease ◽  
Whole Exome ◽  
History Of ◽  
In Trans ◽  
The Common

McArdle disease is a progressive and debilitating glycogen storage disease with typical onset in late childhood. Here we describe a former competitive athlete with early adult onset McArdle disease and a septuagenarian with a history of exercise-intolerance since adolescence who was evaluated for proximal muscle weakness. Exome sequencing identified bi-allelic variants in PYGM gene for both cases. The former athlete has the common, well-known pathogenic variant p.(Arg50Ter) in trans with a novel missense variant, p.(Asp694Glu). The second individual has a previously described homozygous missense variant, p.(Arg771Gln). Here, we describe the clinical course, enzyme-testing results using muscle tissue and molecular findings for the individuals, and add to the knowledge of the genotypic spectrum of this disorder.

Exercise as Treatment for Alcohol Dependence

2013 ◽  
Vol 22 (3-4) ◽  
pp. 205-216 ◽  
Author(s):  
Kirsten K. Roessler ◽  
Randi Bilberg ◽  
Kurt Jensen ◽  
Anne-Sofie Kjaergaard ◽  
Ajla Dervisevic ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Aerobic Power ◽  
Moderate Intensity ◽  
Future Research ◽  
Moderate Intensity Exercise ◽  
Post Intervention ◽  
Testing Environment ◽  
Clinical Observations ◽  
The Social ◽  
Cardio Respiratory Fitness

Abstract Objective The clinical management of alcohol dependence involves evidence-based knowledge on medical treatment, physical training, and psychological management. This pilot study investigates the effect of physical exercise on cardio-respiratory fitness and socio-psychological outcomes. Design: 10 alcohol patients are included to 12 times moderate intensity exercise in groups. Methods: Aerobic power, anxiety, and depression are measured at baseline and post intervention. Observations of the instructor are described. Results: No significant change of aerobic power, but decreased subjective exhaustion. A trend is shown of decreased depression and less concern. Clinical observations showed the testing environment as obstacle and found the communicative role of the instructor crucial. Conclusion: Future research with regard of adherence has to concentrate on the social and contextual aspects of physical activity as treatment.

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