Glycogen Storage Disease Type V (McArdle Disease)
An inherited muscle glycogen phosphorylase deficiency causing exercise intolerance, muscle cramps, and a risk of exertional rhabdomyolysis.
- Autosomal Recessive
- PYGM Gene Deficiency
- Exercise Intolerance Pattern
- Most Common In
- Childhood to adulthood
- Inheritance
- Autosomal Recessive
- Key Gene
- PYGM
- Hallmark Sign
- 'Second Wind' Phenomenon
Condition Overview
Glycogen Storage Disease Type V (McArdle disease) is caused by deficiency of myophosphorylase, the muscle-specific isoform of glycogen phosphorylase, encoded by the PYGM gene. Without this enzyme, skeletal muscle cannot break down glycogen to fuel high-intensity exercise, leading to early fatigue, cramping, and a risk of exercise-induced muscle breakdown.
Unlike GSD I, II, III, and IV, McArdle disease typically does not affect the liver or cause hypoglycemia, since the defect is restricted to the muscle isoform of the enzyme.
Types and Subtypes
McArdle disease is a relatively uniform clinical entity, though severity can vary between individuals.
Symptoms and Signs
Symptoms are triggered specifically by physical exertion.
Causes and Risk Factors
McArdle disease is caused by inherited mutations in the PYGM gene.
Diagnosis and Investigations
Diagnosis relies on a combination of clinical history, exercise testing, and genetic confirmation.
Disease Severity Classification
McArdle disease severity is described by symptom frequency and complication history rather than formal staging.
Standard Treatment
Management centers on activity modification and prompt treatment of acute episodes.
Advanced & Emerging Therapies
No disease-modifying enzyme or gene therapy is currently approved for McArdle disease, but research continues.
Dietary/Metabolic Approaches
Ketogenic and Modified Dietary Strategies
Some studies have explored alternative fuel strategies, such as ketogenic diets, to provide muscle energy without relying on glycogen breakdown.
Gene Therapy
Investigational PYGM Gene Therapy Research
Early preclinical and research efforts are exploring gene therapy approaches to restore myophosphorylase activity.
Biomarkers & Monitoring Parameters
Several markers are used to monitor McArdle disease.
When to Seek a Second Opinion
Specialist input can help optimize quality of life in McArdle disease.
Clinical Trials & Research
Prognosis & Outcomes
McArdle disease is generally compatible with a normal lifespan when activity is managed appropriately.
Supportive Care
Supportive strategies help patients manage daily activity and exercise safely.
How CancerFax Helps You Explore Treatment Options
CancerFax helps individuals with McArdle disease connect with neuromuscular and metabolic specialists, review genetic and exercise test results, and explore current research into dietary and gene-based approaches.
Get a free case reviewFrequently Asked Questions
GSD Type V (McArdle disease) is caused by deficiency of myophosphorylase, the muscle enzyme needed to break down glycogen during exercise, leading to exercise intolerance and muscle cramping.
Early signs often include unusual fatigue, cramping, or muscle pain during brief intense exercise, sometimes noticed first in childhood or adolescence.
It is caused by inherited mutations in the PYGM gene, passed down in an autosomal recessive pattern.
It describes the improved exercise tolerance many patients experience if they briefly rest when symptoms begin, allowing the body to shift to using blood-borne fuels instead of muscle glycogen.
Diagnosis involves creatine kinase testing, a forearm exercise test, and confirmatory PYGM gene sequencing, sometimes supported by muscle biopsy.
It is generally compatible with a normal lifespan, but intense unaccustomed exercise can trigger rhabdomyolysis, which can lead to kidney injury if not managed promptly.
Management focuses on activity pacing, pre-exercise carbohydrate intake, and regular low-to-moderate aerobic conditioning under specialist guidance.
Yes. CancerFax can review your medical reports and genetic test results, help coordinate second opinions with metabolic disease specialists, and assist in exploring enzyme replacement therapy, gene therapy trials, or transplant evaluation at centers in India, China, and internationally.