Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study

Hennis, P. J.; Murphy, Elaine; Meijer, Rick I.; Lachmann, Robin; Ramachandran, Radha; Bordoli, Claire; Rayat, Gurinder; Tomlinson, David

doi:10.1186/s13023-022-02184-1

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…Several manifestations of GSDs can affect functional capacity and activities of daily living, and thereby QoL 89,[130][131][132][133] . These manifestations include muscle weakness, cardiomyopathy, arrhythmia, abdominal distension, short stature and gastrointestinal disturbances.…”

Section: Quality Of Lifementioning

confidence: 99%

Glycogen storage diseases

Hannah,

Derks,

Drumm

et al. 2023

Nat Rev Dis Primers

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Glycogen storage diseases (GSDs) are a group of rare, monogenic disorders that share a defect in the synthesis or breakdown of glycogen. This Primer describes the multi-organ clinical features of hepatic GSDs and muscle GSDs, in addition to their epidemiology, biochemistry and mechanisms of disease, diagnosis, management, quality of life and future research directions. Some GSDs have available guidelines for diagnosis and management. Diagnostic considerations include phenotypic characterization, biomarkers, imaging, genetic testing, enzyme activity analysis and histology. Management includes surveillance for development of characteristic disease sequelae, avoidance of fasting in several hepatic GSDs, medically prescribed diets, appropriate exercise regimens and emergency letters. Specific therapeutic interventions are available for some diseases, such as enzyme replacement therapy to correct enzyme deficiency in Pompe disease and SGLT2 inhibitors for neutropenia and neutrophil dysfunction in GSD Ib. Progress in diagnosis, management and definitive therapies affects the natural course and hence morbidity and mortality. The natural history of GSDs is still being described. The quality of life of patients with these conditions varies, and standard sets of patient-centred outcomes have not yet been developed. The Nature Reviews Disease Primers | (2023) 9:46 2 0123456789();: Primer caused by genetic defects that are associated predominantly with abnormalities of glycogen metabolism and that are recognized in the literature as GSDs, namely, GSD 0a, GSD 0b, GSD I, Pompe disease, GSD III, GSD IV, GSD V, GSD VI, GSD VII, GSD IX, GSD X, GSD XI (lactate dehydrogenase sub unit A deficiency), GSD XII, GSD XIII, phosphoglucomutase 1 deficiency-congenital disorder of glycosylation (PGM1-CDG; previously called GSD XIV), GSD XV, Fanconi-Bickel syndrome (FBS) and phosphoglycerate kinase (PGK) deficiency. Of note, both lactate dehydrogenase subunit A deficiency and FBS are sometimes referred to as GSD XI in the literature. In this Review, GSD XI refers to lactate dehydrogenase subunit A deficiency, and FBS is referred to by eponym.GSDs seem to represent a phenotypic disease continuum. Compelling examples of this continuum include infantile-onset and late-onset Pompe disease and prenatal-onset GSD IV and adult-onset GSD IV, which is also known as adult polyglucosan body disease (APBD). For example, infantile-onset and late-onset Pompe disease have the same mechanism, which is accumulation of glycogen in lysosomes owing to variants in GAA that cause poor function of the GAA enzyme. The severity of disease and clinical manifestations differ between infantile-onset and late-onset disease owing to genotype-phenotype correlation.Owing to the similar disease mechanisms, the differences in severity and presentation reflect a continuum of one disease process. Understanding of the variable expressivity of these rare conditions improved with the identification of more patients with time, increased awareness and improved genetic testing (which...

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Section: Quality Of Lifementioning

confidence: 99%

Glycogen storage diseases

Hannah,

Derks,

Drumm

et al. 2023

Nat Rev Dis Primers

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“…Aerobic capacity is the ability of the cardiorespiratory system to supply sufficient oxygen to peripheral tissues for energy production 1 – 3 . Therefore, it is regarded as an important fitness factor for maintaining and improving health.…”

Section: Introductionmentioning

confidence: 99%

Microbiota influences host exercise capacity via modulation of skeletal muscle glucose metabolism in mice

Kim

et al. 2023

Exp Mol Med

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The microbiota enhances exercise performance and regulates host physiology and energy metabolism by producing beneficial metabolites via bacterial fermentation. In this study, we discovered that germ-free (GF) mice had a reduced capacity for aerobic exercise as well as low oxygen consumption rates and glucose availability. Surprisingly, GF mice showed lower body weight gain and lower fat mass than specific pathogen-free (SPF) mice. Therefore, we hypothesized that these paradoxical phenotypes could be mediated by a compensatory increase in lipolysis in adipose tissues owing to impaired glucose utilization in skeletal muscle. Our data revealed that gut microbiota depletion impairs host aerobic exercise capacity via the deterioration of glucose storage and utilization. The improved browning ability of GF mice may have contributed to the lean phenotype and negatively affected energy generation. These adaptations limit obesity in GF mice but impede their immediate fuel supply during exercise, resulting in decreased exercise performance.

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Mitochondrial Dysfunction in Glycogen Storage Disorders (GSDs)

Mishra,

Kakhlon

2024

Biomolecules

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Glycogen storage disorders (GSDs) are a group of inherited metabolic disorders characterized by defects in enzymes involved in glycogen metabolism. Deficiencies in enzymes responsible for glycogen breakdown and synthesis can impair mitochondrial function. For instance, in GSD type II (Pompe disease), acid alpha-glucosidase deficiency leads to lysosomal glycogen accumulation, which secondarily impacts mitochondrial function through dysfunctional mitophagy, which disrupts mitochondrial quality control, generating oxidative stress. In GSD type III (Cori disease), the lack of the debranching enzyme causes glycogen accumulation and affects mitochondrial dynamics and biogenesis by disrupting the integrity of muscle fibers. Malfunctional glycogen metabolism can disrupt various cascades, thus causing mitochondrial and cell metabolic dysfunction through various mechanisms. These dysfunctions include altered mitochondrial morphology, impaired oxidative phosphorylation, increased production of reactive oxygen species (ROS), and defective mitophagy. The oxidative burden typical of GSDs compromises mitochondrial integrity and exacerbates the metabolic derangements observed in GSDs. The intertwining of mitochondrial dysfunction and GSDs underscores the complexity of these disorders and has significant clinical implications. GSD patients often present with multisystem manifestations, including hepatomegaly, hypoglycemia, and muscle weakness, which can be exacerbated by mitochondrial impairment. Moreover, mitochondrial dysfunction may contribute to the progression of GSD-related complications, such as cardiomyopathy and neurocognitive deficits. Targeting mitochondrial dysfunction thus represents a promising therapeutic avenue in GSDs. Potential strategies include antioxidants to mitigate oxidative stress, compounds that enhance mitochondrial biogenesis, and gene therapy to correct the underlying mitochondrial enzyme deficiencies. Mitochondrial dysfunction plays a critical role in the pathophysiology of GSDs. Recognizing and addressing this aspect can lead to more comprehensive and effective treatments, improving the quality of life of GSD patients. This review aims to elaborate on the intricate relationship between mitochondrial dysfunction and various types of GSDs. The review presents challenges and treatment options for several GSDs.

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Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study

Cited by 3 publications

References 56 publications

Glycogen storage diseases

Glycogen storage diseases

Microbiota influences host exercise capacity via modulation of skeletal muscle glucose metabolism in mice

Mitochondrial Dysfunction in Glycogen Storage Disorders (GSDs)

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