Metabolic Myopathies in Glycogen Storage Disorders

Metabolic myopathies in glycogen storage disorders encompass a group of inherited conditions in which defects in enzymes or transporters of glycogen metabolism impair muscular energy production. The most common example, McArdle disease (glycogen storage disease type V), arises from deficiency of skeletal muscle glycogen phosphorylase, leading to early exertional fatigue, muscle cramps and risk of rhabdomyolysis. Similar disorders include Tarui disease (type VII), due to phosphofructokinase deficiency, and Pompe disease (type II), caused by lysosomal acid alpha-glucosidase deficiency. Clinical manifestations range from exercise intolerance and the characteristic “second wind” phenomenon, to progressive weakness and fixed myopathy in severe cases. Diagnosis relies on a combination of clinical history, exercise testing, muscle biopsy and genetic analysis. Current management strategies focus on tailored exercise programmes, dietary interventions that provide alternative fuel substrates and supportive care to minimise muscle damage. Advances in patient registries and cellular modelling are improving understanding of genotype–phenotype correlations and paving the way for novel therapies.

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Metabolic Myopathies in Glycogen Storage Disorders publication trend

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Technical terms

Metabolic myopathy: A muscle disorder caused by defects in biochemical pathways responsible for energy production.
Glycogen storage disorder (GSD): A genetic condition in which an enzyme defect leads to abnormal glycogen synthesis or breakdown.
McArdle disease: GSD type V, characterised by skeletal muscle glycogen phosphorylase deficiency.
Second wind phenomenon: An improvement in exercise tolerance after a brief rest, due to enhanced delivery of alternative fuels to muscle.
Induced pluripotent stem cell (iPSC): A reprogrammed somatic cell capable of differentiating into multiple cell types, used for disease modelling.
Ketogenic diet: A high-fat, low-carbohydrate dietary regimen that induces ketosis and promotes fat oxidation as an energy source.

References

1. Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study. Clinical Nutrition (2023).
2. Carbohydrate Ingestion before Exercise for Individuals with McArdle Disease: Survey Evidence of Implementation and Perception in Real-World Settings. Nutrients (2024).
3. Creation of an iPSC-Based Skeletal Muscle Model of McArdle Disease Harbouring the Mutation c.2392T>C (p.Trp798Arg) in the PYGM Gene. Biomedicines (2023).