Myophosphorylase Deficiency (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. Another name for McArdle disease is glycogen storage disease GSD 5 or GSD V.

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 up 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 up 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.

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 usually passes down from a parent to a child. You generally have a pair of genes (1 from each parent) for each substance your body makes. In most cases, a person with McArdle disease needs to have 2 copies of a mutated gene. This is recessive inheritance.

A person who has only 1 copy of the mutated gene may still have some 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 does not 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.

• 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.

Your healthcare provider first takes a health history. He or she asks about your recent symptoms, past health conditions, and your family health history. He or she usually does a thorough physical exam, including tests of your muscle strength. He or she 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 do not receive the diagnosis until later in adulthood.

McArdle disease is a rare muscle disorder. Muscle cells can’t store energy well. Energy in muscles is stored as glycogen. McArdle disease is one of a group of diseases called glycogen storage diseases. The symptoms often appear in childhood. But some people are not diagnosed until later as an adult.

There is no cure for McArdle disease. Diet and exercise changes can help control it. A low or moderate exercise routine may help. This lets your body get the most out of your ability to use glucose. It is very important to work with your healthcare team to create an exercise plan. Getting too much exercise can harm your muscles and kidneys. Your care plan may also include:

• Carefully watching how many carbohydrates you eat.

• Eating or drinking certain amounts of sugar before exercise.

• Not doing intense exercise.

• Following a safe, moderate aerobic exercise plan.

• Taking vitamin B-6 supplements.

• Taking creatine supplements.

• A diet high in protein.

• Taking other medicines, such as angiotensin-converting enzyme (ACE) inhibitors.

• Not taking certain medicines, such as statins.

People with McArdle disease are at risk for muscle tissue decay after a lot of physical activity. This is known as rhabdomyolysis. When muscle tissue decays, it often releases myoglobin. This can cause dark brownish red urine (myoglobinuria). This may lead to kidney failure in some people. Other possible complications of McArdle disease include:

• Permanent muscle weakness (rare).

• Higher risk for problems from general anesthesia.

• Higher risk for problems from cholesterol-lowering medicines (statins).