McArdle Disease

Overview

McArdle disease, also called glycogen storage disease type V, is an inherited muscle disorder. Muscles store sugar in the form of glycogen and break it down rapidly to release energy during exercise. People with McArdle disease are missing a working version of the enzyme myophosphorylase, which is needed for that first step of glycogen breakdown. As a result, their muscles cannot tap into this important energy source, especially during the early minutes of activity or intense effort.

The condition is a type of metabolic myopathy. It typically appears in childhood or early adulthood, with people noticing that their muscles tire, ache, and cramp soon after starting exercise. A distinctive feature is the "second wind" phenomenon, where symptoms ease after a short rest as the body switches to other fuels. Although there is no cure, understanding and adapting exercise can greatly improve daily life.

Symptoms

Symptoms center on the muscles and their response to exertion.

• Exercise intolerance: Muscle fatigue, pain, and cramping within the first minutes of activity, especially with intense effort like lifting or sprinting.
• The "second wind" phenomenon: If a person rests briefly when symptoms start and then resumes gentle activity, exercise often becomes easier as the body uses fat and blood sugar for fuel.
• Muscle cramps and stiffness: Sometimes with painful contractures where the muscle locks up.
• Dark urine after exercise: Cola-colored urine signals rhabdomyolysis, the breakdown of muscle tissue, which can affect the kidneys.
• Weakness: Some people develop fixed muscle weakness later in life.

Causes

McArdle disease is caused by inherited mutations in the gene that provides instructions for the muscle enzyme myophosphorylase.

• Enzyme deficiency: Without working myophosphorylase, muscle cannot break down its stored glycogen to fuel rapid or intense activity.
• Autosomal recessive inheritance: A child must inherit a faulty gene copy from both parents to develop the disease; parents who each carry one copy are usually unaffected carriers.

Because the body can still use fats and blood glucose for energy, problems are most pronounced during the early and most demanding phase of exercise, before these alternative fuels become available.

Risk Factors

• A family history of McArdle disease or unexplained exercise intolerance
• Parents who are both carriers of the gene change
• Intense or sudden bursts of exercise, sustained isometric effort (like carrying heavy loads), and exercising without a warm-up, all of which can provoke severe cramps and muscle breakdown

Diagnosis

Diagnosis is based on the characteristic history of exercise intolerance and a second wind, confirmed with testing.

• Blood tests: Creatine kinase, a muscle enzyme, is usually elevated even at rest.
• Exercise testing: A forearm exercise test shows that lactate does not rise normally because glycogen cannot be broken down.
• Muscle biopsy: Can show glycogen buildup and absent myophosphorylase enzyme activity.
• Genetic testing: Confirms the diagnosis by identifying mutations in the responsible gene and is increasingly the preferred method.

Treatment

There is no cure, but careful management of exercise and fuel can substantially reduce symptoms and the risk of muscle breakdown.

• Warm up gradually: Starting activity slowly allows the body to reach its "second wind" and switch to alternative fuels, making exercise more comfortable and safer.
• Pre-exercise carbohydrate: A small amount of carbohydrate before activity can improve tolerance in many people.
• Regular moderate aerobic exercise: Improves fitness and the body's ability to use fat for fuel, but should be built up gently.
• Avoiding high-intensity bursts: Limiting sudden, maximal, or sustained isometric efforts that trigger cramps and muscle damage.
• Staying hydrated and recognizing warning signs: Stopping activity and seeking care if severe cramps or dark urine develop.
• Specialist guidance: An individualized plan and genetic counseling for families.

Prevention

The disorder cannot be prevented, but dangerous episodes of muscle breakdown often can.

• Always warm up slowly and pace yourself into the "second wind"
• Avoid sudden maximal effort and prolonged heavy lifting or gripping
• Consider a small carbohydrate snack before planned exercise, as advised
• Stay well hydrated, especially in hot weather
• Stop and rest at the first sign of severe cramping, and seek care for dark urine

When to See a Doctor

See a doctor if you regularly experience muscle pain, cramps, or fatigue soon after starting exercise, particularly if you notice a second wind or have a family history. Seek urgent medical care if you have:

• Dark red, brown, or cola-colored urine after exercise, a sign of muscle breakdown that can harm the kidneys
• Severe, persistent muscle pain or swelling
• A muscle that locks up and will not relax
• Feeling very unwell after intense exertion

Rhabdomyolysis needs prompt evaluation and fluids to protect kidney function.

Related Topics

Frequently Asked Questions

References

1. National Institute of Neurological Disorders and Stroke (NINDS).
2. Muscular Dystrophy Association. McArdle Disease.
3. MedlinePlus, U.S. National Library of Medicine. Glycogen storage disease type V.
4. National Organization for Rare Disorders (NORD).