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.

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.

Sodium valproate for McArdle disease (glycogen storage disease type V – GSDV)

2015 ◽  
Vol 25 ◽  
pp. S220-S221 ◽  
Author(s):  
R. Scalco ◽  
C. Vissing ◽  
R. Godfrey ◽  
S. Chatfield ◽  
N. Løkken ◽  
...  
Keyword(s):  
Sodium Valproate ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Mcardle Disease ◽  
Type V

scholarly journals A First Case Report Of Mcardle Disease And Alive Kidney Transplantation

2021 ◽  
Author(s):  
Ramazan Danis ◽  
Jehat Kılıc ◽  
Delyadıl Karakaş KILIÇ ◽  
emrah günay ◽  
nurettin ay ◽  
...  
Keyword(s):  
Skeletal Muscles ◽  
Storage Disease ◽  
Glycogen Metabolism ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Mcardle Disease ◽  
First Case ◽  
Before And After ◽  
Type V

McArdle disease (Glycogen storage disease type V, GSDV ) is an inherited disorder of glycogen metabolism affecting only skeletal muscles. A 56-year-old male patient with McArdle disease had the symptoms such as fatigue, muscle weakness since he was 8 years old in his history. A Pre-emptive kidney transplant from his wife was performed on the patient who has gone through rhabdomyolysis attacks during his life period. As far as known, this is the first case in the literature. We aim to share this process before and after the transplantation.

scholarly journals The Phenotypic and Genetic Spectrum of Glycogen Storage Disease Type VI

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1205
Author(s):  
Sarah Catharina Grünert ◽  
Luciana Hannibal ◽  
Ute Spiekerkoetter
Keyword(s):  
Liver Cirrhosis ◽  
Glycogen Storage Disease ◽  
Glycogen Phosphorylase ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Hepatic Glycogen ◽  
Laboratory Findings ◽  
Poor Growth

Glycogen storage disease type VI (GSD VI) is an autosomal recessive disorder of glycogen metabolism due to mutations in the glycogen phosphorylase gene (PYGL), resulting in a deficiency of hepatic glycogen phosphorylase. We performed a systematic literature review in order to collect information on the clinical phenotypes and genotypes of all published GSD VI patients and to compare the data to those for GSD IX, a biochemically and clinically very similar disorder caused by a deficiency of phosphorylase kinase. A total of 63 genetically confirmed cases of GSD VI with clinical information were identified (median age: 5.3 years). The age at presentation ranged from 5 weeks to 38 years, with a median of 1.8 years. The main presenting symptoms were hepatomegaly and poor growth, while the most common laboratory findings at initial presentation comprised elevated activity of liver transaminases, hypertriglyceridemia, fasting hypoglycemia and postprandial hyperlactatemia. Liver biopsies (n = 37) showed an increased glycogen content in 89.2%, liver fibrosis in 32.4% and early liver cirrhosis in 10.8% of cases, respectively. No patient received a liver transplant, and one successful pregnancy was reported. Our review demonstrates that GSD VI is a disorder with broad clinical heterogeneity and a small number of patients with a severe phenotype and liver cirrhosis. Neither clinical nor laboratory findings allow for a differentiation between GSD VI and GSD IX. Early biochemical markers of disease severity or clear genotype phenotype correlations are missing. Given the overall benign and unspecific phenotype and the need for enzymatic or genetic analyses for confirmation of the diagnosis, GSD VI is likely underdiagnosed. With new treatment approaches in sight, early, pre-symptomatic diagnosis, especially with respect to hepatic cirrhosis, will become even more important.

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