McArdle Disease (Glycogen Storage Disease Type V)

Why McArdle disease causes symptoms

Muscles store energy as glycogen. During the first minutes of exercise, and during intense effort, they rely on breaking glycogen down into glucose. In McArdle disease, the PYGM gene does not produce working myophosphorylase, so muscles cannot access this stored fuel.

At the start of exercise, muscles quickly run short of energy, causing pain, fatigue and stiffness. If the person keeps pushing, muscle fibers can be damaged and release myoglobin and creatine kinase (CK) into the blood (rhabdomyolysis), and myoglobin can damage the kidneys, causing acute kidney injury.

The second wind

After roughly 8 to 10 minutes of low-intensity activity, increased blood flow brings glucose and fatty acids from the bloodstream to the muscles. The heart rate falls and exercise becomes noticeably easier. This second wind phenomenon is characteristic of McArdle disease and helps diagnosis and day-to-day management.

Symptoms

• muscle pain, heaviness and fatigue within minutes of starting activity
• cramps and contractures: painful, prolonged muscle tightening that can last hours
• rapid heart rate and breathlessness at the start of exercise
• dark urine (myoglobinuria) after overexertion, in about half of people at some point
• mild fixed weakness in some older adults, especially around the shoulders
• symptoms provoked by intense short efforts (sprinting, lifting) and by sustained effort (climbing stairs, carrying shopping, walking uphill)

Symptoms usually begin in childhood but are often dismissed as laziness or being unfit. Many people are diagnosed in their 20s or 30s, after an episode of rhabdomyolysis.

Inheritance

McArdle disease is autosomal recessive: a person must inherit two non-working copies of PYGM, one from each parent. Parents are usually healthy carriers. Each child of two carriers has a 25% chance of being affected.

Diagnosis

• Creatine kinase (CK): usually raised even at rest.
• Genetic testing for PYGM variants: the preferred confirmatory test. A common variant (p.R50X) is found in many people of European descent.
• Non-ischemic forearm exercise test: lactate fails to rise while ammonia rises excessively.
• 12-minute walk test or cycle test: demonstrates the second wind with a drop in heart rate after 8 to 10 minutes.
• Muscle biopsy: shows absent myophosphorylase activity and glycogen accumulation. Now used less often.
• Urine and kidney tests after episodes of dark urine.

Other conditions with exercise intolerance, such as other metabolic myopathies, carnitine palmitoyltransferase II deficiency and muscular dystrophies, are considered.

Management

There is no cure, but people can live active lives.

Exercise

• Warm up gradually: start very gently and build up over 10 to 15 minutes until the second wind arrives.
• Regular aerobic exercise such as walking or cycling at moderate intensity improves fitness and reduces symptoms over time.
• Avoid sudden sprints, heavy lifting, isometric efforts (holding heavy objects, pushing a car) and exercise to exhaustion.
• Stop or slow down at the first sign of pain or stiffness, and rest briefly.

Diet and sugar

• A drink containing simple sugar (for example a sports drink) taken 5 to 10 minutes before planned activity can improve exercise tolerance. It is not recommended routinely all day, because of weight gain.
• A diet balanced in complex carbohydrates is generally advised. Other diets have been studied with limited evidence.

Safety measures

• wear a medical alert bracelet
• drink plenty of fluids after strenuous activity to protect the kidneys
• tell surgeons and anesthetists about McArdle disease. Tourniquets and some anesthetic practices need care
• treat dark urine as an emergency
• statins may worsen muscle symptoms. Discuss with your doctor

Outlook

McArdle disease is one of several types of glycogen storage disease. It does not shorten life when episodes of severe rhabdomyolysis are avoided. Many people improve their exercise tolerance through regular, well-planned aerobic training. Some develop mild permanent weakness later in life. Kidney injury from rhabdomyolysis is the main serious risk and is preventable.

Frequently asked questions

What is McArdle disease?

McArdle disease, or glycogen storage disease type V, is a rare inherited condition in which muscles lack the enzyme myophosphorylase and cannot use stored glycogen for energy. It causes muscle pain, fatigue and cramps early in exercise.

What is the second wind in McArdle disease?

The second wind is the marked improvement in exercise tolerance after about 8 to 10 minutes of slow, gentle activity. By then, more blood flow delivers glucose and fats to the muscles, allowing exercise to continue more comfortably.

Why does McArdle disease cause dark urine?

Pushing muscles beyond their limits damages muscle fibers, which release myoglobin into the bloodstream. Myoglobin passes into the urine and colors it dark brown or red. This is called rhabdomyolysis and can harm the kidneys, so it needs urgent care.

Can people with McArdle disease exercise?

Yes, and regular moderate aerobic exercise is recommended. Start slowly, warm up until the second wind arrives, and avoid sudden intense or heavy lifting efforts. With careful training, many people significantly improve their fitness.

How is McArdle disease diagnosed?

Doctors look for a raised resting CK level, a history of exercise intolerance and the second wind, then confirm with genetic testing for PYGM gene variants. A forearm exercise test or muscle biopsy is sometimes used.