McArdle Disease (GSD5)

What is McArdle disease?

McArdle disease is a genetic (inherited) condition that mainly affects your skeletal muscles — the muscles that allow you to move. It’s also called glycogen storage disease type 5 (GSD5).

McArdle disease happens when you have a deficiency or complete lack of an enzyme called muscle glycogen phosphorylase (myophosphorylase). This issue causes symptoms like painful muscle cramps and weakness, especially during physical activity.

McArdle disease most often becomes apparent in your teens, 20s or 30s, but it can develop at any age. The condition gets its name from Dr. Brian McArdle, who first reported it in 1951.

How common is McArdle disease?

McArdle disease is rare. Researchers estimate that it affects 1 in 50,000 to 1 in 200,000 people in the United States.

What are the symptoms of McArdle disease?

The symptoms of McArdle disease can vary widely in severity from person to person.

The most common symptom is getting tired easily from physical activity (exercise intolerance). Other symptoms of McArdle disease include:

• Muscle cramps.
• Weakness.
• Fatigue.
• Muscle pain.
• Muscle stiffness.

All these symptoms are much more apparent soon after starting physical activity. They typically get better once you rest. Resting after initial fatigue may lead to a “second wind” — you can better handle physical activity if you start it again. People with McArdle disease usually don’t have symptoms between episodes of physical activity.

You may be able to tolerate light-to-moderate exercise, like walking on level ground. But strenuous physical activity usually brings on symptoms quickly. Exercises that involve squeezing your muscles without any movement (isometric exercises), like lifting heavy objects, squatting or standing on your tiptoes can cause muscle damage.

What are the complications of McArdle disease?

About half of people with McArdle disease experience rhabdomyolysis (muscle breakdown) after strenuous physical activity. This is a life-threatening condition that can cause acute (sudden and severe) kidney failure and dangerous hyperkalemia (high potassium).

It’s important to be mindful of how much — and hard — you exercise to try to prevent rhabdomyolysis. Get immediate medical help if you develop symptoms, like muscle swelling and dark pee that’s brown, red or tea-colored.

What causes McArdle disease?

McArdle disease is a genetic (inherited) condition. Specifically, mutations (changes) in the PYGM gene cause it. Normally, the PYGM gene provides instructions for your body to make an enzyme called myophosphorylase (muscle glycogen phosphorylase).

This enzyme, which is only in your skeletal muscle cells, breaks down glycogen (stored glucose in your muscles) into glucose-1-phosphate. Additional body processes then convert glucose-1-phosphate into glucose. Glucose is a simple sugar that’s your body’s main source of energy. Your muscles use lots of glucose when you’re physically active.

PYGM gene changes result in a deficiency or complete lack of myophosphorylase, which means your muscle cells can’t break down glycogen effectively. Because your muscle cells can’t produce enough energy (glucose) to use, they become tired easily.

So far, researchers have found 179 variants that affect the PYGM gene.

McArdle disease inheritance pattern

You inherit McArdle disease from your biological parents in an autosomal recessive pattern. This means that both of your parents passed on the altered gene (they’re carriers). People who are just carriers of the altered gene typically don’t have symptoms of the condition.

How is McArdle disease diagnosed?

Healthcare providers mainly use a forearm exercise test to diagnose McArdle disease. It involves taking blood samples from your forearm before and after doing brief physical activity. Specifically, the blood tests check lactic acid and ammonia levels.

If you have a lack of a rise in lactic acid levels during the test, it may mean you have McArdle disease. Typically, lactic acid levels would be three times higher after the exercise compared to before it.

Other tests providers use to help diagnose the condition include:

• Creatine kinase blood test: Your muscles release creatine kinase (CK) into your blood when they’re damaged. People with McArdle disease typically have chronically elevated CK levels.
• Graded exercise stress test: This can test the “second wind” phenomenon, which is common in McArdle disease. Your provider may have you do bouts of physical activity followed by rest to see if resting gives you a “second wind” and you’re able to better tolerate the activity.
• Muscle biopsy: During this test, a provider takes a small sample of your skeletal muscle and sends it to a lab for analysis under a microscope. A pathologist will look for signs of McArdle disease in the tissue.
• Genetic testing: This may be able to identify a specific genetic variant that causes McArdle disease.

What is the treatment for McArdle disease?

There’s no cure for McArdle disease. Treatment mainly involves avoiding the types of physical activity that make your symptoms worse. However, a total lack of physical activity can also be harmful to your health.

Studies show that moderate-intensity graded aerobic exercise therapy can be beneficial to people with McArdle disease. People who use this type of physical activity have a significant decrease in exercise intolerance and experience the “second wind” phenomenon sooner during activity. You’ll work with your healthcare provider and a physical therapist to find the best exercise therapy plan for you.

Studies also show that having a high-carbohydrate eating plan can help lessen symptom severity during activity. This can help your muscles get energy from blood glucose (sugar) instead of from muscle glycogen. Your provider or a registered dietitian may recommend getting:

• 65% of your calorie intake from complex carbohydrates (like those found in vegetables, fruits, bread, pasta and rice).
• 20% of your calories from fat.
• 15% of your calories from protein.

Consuming simple sugars right before exercise (like a sports drink containing sugar, for example) may also help.

Can I prevent McArdle disease?

As McArdle disease is genetic, there’s nothing you can do to prevent it.

If you’re concerned about the risk of passing on McArdle disease or other genetic conditions before trying to have a biological child, talk to your healthcare provider about genetic counseling.

What can I expect if I have McArdle disease?

Most people with McArdle disease lead a typical life. Some people experience persistent weakness and muscle atrophy later in life — usually in their 60s or 70s.

It’s important to be aware of the signs of rhabdomyolysis and avoid triggering it as much as possible. This is the main complication of McArdle disease.

What is the life expectancy of someone with McArdle disease?

McArdle disease typically doesn’t affect life expectancy.

There’s a very rare form of the condition called infantile McArdle syndrome that appears shortly after birth. This form is fatal — the symptoms are severe and rapidly get worse.

When should I see my healthcare provider about McArdle disease?

If your symptoms get worse or your ability to do physical activities you regularly do changes, see your healthcare provider.

You may need to see a physical therapist and/or dietitian regularly for guidance on your treatment plan.

When should I go to the ER?

If you have symptoms of rhabdomyolysis, go to the ER as soon as possible. Symptoms include:

• Muscle swelling.
• Weak muscles.
• Tender and sore muscles.
• Dark pee that’s brown, red or tea-colored.
• Dehydration.
• Decreased urination.
• Nausea.
• Loss of consciousness.

A note from Cleveland Clinic

McArdle disease can make it difficult to do certain physical activities. But the good news is that it’s manageable and otherwise doesn’t affect your overall health. Your healthcare provider will work with you to find a treatment plan that’s best for you.