What is McArdle disease?

McArdle disease is a rare muscle disorder. In this disease, the muscle cells can’t break down a complex sugar called glycogen. It is part of a group of diseases called glycogen storage diseases. Other names for McArdle disease are glycogen storage disease type 5 (GSD 5 or GSD V) and myophosphorylase deficiency.

Your cells use a simple sugar, called glucose, for energy. When you eat, your digestive system sends a large amount of glucose into your blood. This raises your blood glucose levels. Your body removes this extra glucose from the blood to stabilize the blood glucose level. Your body then converts the extra glucose into glycogen. It stores it in the liver, muscles, and other places in the body. Glycogen is a form of energy storage.

When you haven’t eaten in a while, the glucose level in your blood starts to drop. This tells your body to start using some of the glycogen it saved earlier. The glycogen gets broken down into the glucose so that your body has a steady supply.

Your muscles need a constant supply of glucose to keep working well. In McArdle disease, your muscles can’t break down the saved glycogen. That's because an important substance needed for that process is missing from your muscle cells. This means your muscles can’t use the stored glycogen to get the glucose they need. The key missing substance in your muscles is an enzyme called myophosphorylase. An enzyme is a substance that helps speed up chemical reactions in the body.

This may make it hard for you to exercise without becoming tired and having muscle pain. Most of the time, symptoms of this health problem appear by the time a person is age 15.

What causes McArdle disease?

McArdle disease is an inherited disease. It results from changes (mutations) in the gene for the enzyme muscle phosphorylase. Your muscle cells can’t make this enzyme. So they can’t break down glycogen into glucose. Your muscles need glucose to work their best.

The gene change that causes McArdle disease often passes down from a parent to a child. You generally have a pair of genes (one from each parent) for each substance your body makes. In most cases, a person with McArdle disease needs to have two copies of a mutated gene. This is recessive inheritance.

A person who has only one copy of the mutated gene may still have some symptoms of McArdle disease.

What are the symptoms of McArdle disease?

McArdle disease causes muscle symptoms. Generally, it can make it hard for you to exercise without becoming tired. You may find that this doesn't happen with gentle walking. But you may have trouble with strenuous exercise for more than a few minutes. You may notice that after a brief rest you feel a “second wind” that lets you exercise again. These symptoms can vary in intensity. Some common symptoms of McArdle disease are:

• Better able to do aerobic exercise after 8 to 10 minutes (second wind phenomenon)

• Brownish red urine, especially after periods of activity

• Easily tiring during activity, with stiffness or weakness soon after starting exercise

• Muscle cramping

• Muscle pain

• Lasting (permanent) weakness in the thigh or other muscles. This happens in a small portion of people with the condition.

Most of the time, people notice these symptoms before age 15. Often, people assume the symptoms are “growing pains” or due to some other cause. Different people may have symptoms of different severity. You may even notice that the symptoms seem worse or better at different times.

How is McArdle disease diagnosed?

Your healthcare provider first takes a health history. They ask about your recent symptoms, past health conditions, and your family health history. They usually do a thorough physical exam, including tests of your muscle strength. They may test your endurance or ability for sustained exercise. Some diagnostic tests include:

• Blood tests to check for muscle enzymes, such as creatine kinase

• DNA blood tests for known McArdle disease mutations

• Electromyography to measure the electrical activity of the muscles

• Forearm exercise test

• MRI studies of your muscles

• Muscle biopsy to examine the muscle cells for glycogen buildup

• Urine tests to check for myoglobin, which darkens the urine

You may first see your main healthcare provider who may then refer you to a specialist, such as a neurologist. While the symptoms often appear in childhood, McArdle disease is rare. Some people with the condition don't receive the diagnosis until later in adulthood.

How is McArdle disease treated?

There is no cure for McArdle disease. But you may be able to use certain diet and exercise strategies to help control the problem. A well-designed low or moderate exercise routine may help your body get the most out of your ability to use glucose. It is very important to work with your healthcare provider to create this plan. Overdoing exercise can harm the muscles and kidneys in people with McArdle disease. You can work with your healthcare team to create the best care plan for your situation. Some therapies used to help manage McArdle disease are:

• Careful attention to a diet rich in carbohydrates

• Creatine supplements

• Eating or drinking prescribed amounts of sucrose before exercise

• Prescribed, moderate aerobic exercise plan

People with McArdle disease need to work with their care team to establish a safe exercise plan. For more information and support, you may also want to talk with the team about genetic counseling.

Key points about McArdle disease

• McArdle disease (GSD 5) is a rare, genetic muscle disorder. It is an inherited disease.

• It is a type of glycogen storage disease. It results from a lack of a key substance that the muscles need to break down glycogen into sugar (glucose) for energy.

• The condition causes tiredness and muscle pain during exercise.

• The disease can lead to dark urine. Severe, uncontrolled McArdle disease can cause life-threatening kidney problems.

• You can work with your care team to make a diet and exercise plan that helps you control McArdle disease and its complications.

Next steps

Tips to help you get the most from a visit to your healthcare provider:

• Know the reason for your visit and what you want to happen.

• Before your visit, write down questions you want answered.

• Bring someone with you to help you ask questions and remember what your healthcare provider tells you.

• At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.

• Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.

• Ask if your condition can be treated in other ways.

• Know why a test or procedure is recommended and what the results could mean.

• Know what to expect if you do not take the medicine or have the test or procedure.

• If you have a follow-up appointment, write down the date, time, and purpose for that visit.

• Know how you can contact your healthcare provider if you have questions, especially after office hours and on weekends.