McArdle disease

McArdle disease, also known as glycogen storage disease type V (GSDV), is a rare inherited metabolic muscle disease, which happens when the body doesn’t have enough of an enzyme called muscle glycogen phosphorylase. This can cause muscle discomfort, weakness, and fatigue during physical activity. A muscle contracture can also occur with strenuous activities and can lead to muscle damage.

Symptoms of McArdle disease are usually present from a young age, often affecting children during physical education (PE) activities at school. The condition can affect skeletal muscle, which are the muscles used for movement. Because McArdle disease is rare, many people aren’t diagnosed until they’re adults.

Exercise intolerance

People with McArdle disease experience exercise intolerance, meaning they tire easily during physical activity. Muscle discomfort and fatigue often happen within the first few minutes of starting aerobic exercise, such as walking. To manage this, those affected will need to slow down their pace or briefly stop. After several minutes of walking, a “second wind” occurs – this allows muscles to start burning fat, which makes it easier to continue the aerobic activity at the same pace without difficulty. However, if the intensity of the activity increases – such as walking uphill or faster – the symptoms can return, and there is a need to slow down or stop and start again.

Myoglobinuria

Strenuous activities like running, squatting, or lifting heavy items, can cause symptoms to appear within seconds. This can lead to muscle contractures (similar to a cramp), causing severe muscle pain, swelling, and myoglobinuria – a dark brown or black discolouration of the urine. Myoglobinuria happens when muscle fibres break down and release myoglobin into the bloodstream, which can potentially lead to kidney damage. This is known as acute kidney injury. The darker the urine, the more severe the muscle injury. Passing dark brown or black urine requires a visit to the nearest Accident and Emergency hospital department (A&E) for blood tests and intravenous fluids. Urine that is lighter in colour can usually be managed at home by increasing fluid intake. Severe swelling of a limb should also prompt a visit to A&E to rule out compartment syndrome, where swelling restricts blood flow to a limb.

Kidney injury from myoglobinuria is reversible and can be prevented with intravenous fluids. In some cases, dialysis may be required to remove waste products from the body – dialysis often involves diverting blood to a machine to be cleaned. It’s crucial to seek medical help as soon as possible to avoid complications.

Muscle weakness

As people with McArdle disease get older, mild muscle weakness can develop, particularly in the shoulder and spine. The severity of muscle weakness varies, but for most people it’s mild.

Eyes

Older people with McArdle disease can develop a rare eye condition called pattern retinal dystrophy. This condition affects the retina and can cause changes to vision. It’s recommended that people over the age of 50 with McArdle disease have their eyes checked every year.

Gout

Gout is more common in people with McArdle disease. Gout is a type of arthritis that causes inflamed swollen joints and sudden, severe joint pain. If a joint (most commonly the big toe) becomes swollen and painful, it’s important to see a GP as soon as possible for anti-inflammatory medication. Recurrent episodes of gout can be prevented with medication such as allopurinol.

Genetic changes

McArdle disease is caused by changes in the PYGM gene. This gene helps produce the muscle glycogen phosphorylase enzyme, which breaks down glycogen (stored glucose) in muscles cells into glucose that can be used for energy. People with McArdle disease don’t have enough of this enzyme. This means there is little energy supply for the muscles when they take part in physical activity.

Inheritance

McArdle disease is inherited in an autosomal recessive pattern. This means people with McArdle disease will have inherited two copies of the changed gene, one from each parent.

For more information, see our inheritance and genetics page.

A diagnosis of McArdle disease typically starts with a referral from a GP to a neurologist or metabolic specialist, who will review symptoms and recommend tests. A neurologist is a doctor who specialises in conditions that affect the muscles and nervous system. A metabolic specialist focuses on conditions related to metabolism, the process that converts food into energy.

A physical examination is usually undertaken. McArdle disease is suspected when someone experiences exercise intolerance and has high levels of creatine kinase (CK) in their blood. In some cases, a person may have drooping eyelids (ptosis) or enlarged calf muscles (pseudohypertrophy). The diagnosis is usually confirmed through genetic testing. If genetic testing doesn’t show definite results, a muscle biopsy may be performed to assess enzyme activity. A forearm exercise test can also be carried out but is not essential.

For more information, see our diagnosis page.

A multi-disciplinary approach, where healthcare professionals work together as a team, is important in not only managing the condition and symptoms, but in improving wellbeing too.

Access to a healthcare team

People with McArdle disease should have access to a multi-disciplinary healthcare team experienced in managing this condition. If you don’t have contact with a specialist team, speak to your GP about getting access.

There is a highly specialised service for people with McArdle disease and related disorders at The National Hospital for Neurology and Neurosurgery (NHNN) in London. The service accepts referrals from children and adults across the UK, but funding may be needed in some areas.

Exercise and physiotherapy

Staying aerobically fit and maintaining a healthy body weight is the best way to help muscles perform better and improve quality of life. It also helps improve the ability to develop a “second wind”, which can improve exercise tolerance.

It’s important to slow down or stop exercising for a few moments if experiencing discomfort or fatigue. High-intensity exercises such as weightlifting or sprinting are to be avoided, as they can cause muscle damage. Similarly, isometric activities such as squatting, crouching, or tensing muscles tightly can quickly cause muscle damage and should be avoided.

“Second wind” phenomenon

When starting an aerobic activity, such as walking, the body first uses glycogen which is stored in muscle cells for energy. People with McArdle disease can’t break this glycogen down to use as an energy source, which is why they develop symptoms. After about eight to nine minutes of walking, the body brings a supply of glucose from the liver to the muscles. This allows people with McArdle disease to burn fat and improves their symptoms.

The “second wind” can only be achieved with aerobic activities. It does not happen when performing more strenuous activities. This phenomenon is more effective in people who are aerobically fit. It’s important to discuss exercise plans with a physiotherapist or other healthcare professionals who have expertise in McArdle disease. They can provide expert advice on safe exercises and on how to improve overall fitness. Gentle aerobic exercises, such as walking and swimming, are recommended.

Diet

There is no evidence that changing diet helps. However, gaining weight or becoming obese can make physical activity more difficult and increase the risk of muscle damage. Staying hydrated, especially during exercise, may be helpful.

Anaesthesia stops a person feeling pain during a procedure or surgery. It’s unclear if people with McArdle disease have a higher risk of complications with general anaesthesia. Some cases of complications have been reported, while on the other hand many people who are diagnosed late in life have had general anaesthesia without complications. It’s important to discuss any surgical procedure with the consultant and the anaesthetist beforehand.