McArdle disease (glycogen storage disease type 5): symptoms, diagnosis and exercise

McArdle disease is one of the glycogen storage diseases, a group of inherited metabolic conditions in which glycogen, the body’s stored form of sugar, cannot be used normally. Patient.info’s professional reference explains that most people with McArdle disease have undetectable myophosphorylase activity and are therefore unable to release glucose from glycogen in muscle. Other names include myophosphorylase deficiency, muscle phosphorylase deficiency and glycogen storage disease type V.

The gene involved, PYGM, is inherited in an autosomal recessive way, which the same source explains means that people with one altered copy are asymptomatic. The result is a muscle that runs short of fuel in the first minutes of activity.

The condition is named after Brian McArdle, who first described it in 1951. Because the faulty enzyme is in skeletal muscle, the main problems affect muscle rather than the liver or other organs.

Patient.info’s reference says people typically experience reversible exercise intolerance, fatigue and acute crises, meaning severe fatigue and painful muscle cramps, sometimes with rhabdomyolysis and dark urine (myoglobinuria). These can be triggered by static muscle contractions such as lifting weights or by dynamic exercise such as climbing stairs or running. Clinical examination between episodes can be normal.

A characteristic feature is the “second wind” phenomenon. After a period of careful pacing or rest, the reference says, the initial pain usually subsides in less than a minute, and after about 8 minutes most patients achieve a second wind and can then continue exercise with less difficulty. It notes this is universal to all patients, although some may not recognise it.

AGSD-UK says that in middle or old age some people experience fixed muscle weakness, possibly from cumulative muscle damage, and lists secondary features such as raised urate level, possible muscle wasting and a risk of acute renal failure.

Patient.info’s reference says that if an episode of myoglobinuria occurs, the patient should drink plenty of fluids, and that the patient should seek medical attention immediately if they feel unwell or stop producing urine. AGSD-UK highlights that continuing activity while in pain risks rhabdomyolysis, which can lead to acute kidney failure.

If you have McArdle disease and develop severe muscle pain, very dark urine or reduced urine, or feel generally unwell after exertion, get medical help promptly and tell the staff about your diagnosis; NHS 111 can advise, and 999 or A&E is appropriate if you are seriously unwell. Your specialist team can tell you what plan they recommend for emergencies.

It is also worth telling anaesthetists about the condition before any operation. Patient.info’s reference says anaesthetists should be made aware, may choose to avoid certain anaesthetic agents, and that tourniquets should not be used during operative procedures.

Diagnosis is suggested by the history. Patient.info’s reference says creatine kinase levels are elevated in more than 90% of patients at rest, and that a history of painful cramps within minutes of starting activity, together with a raised creatine kinase, is highly suggestive. Blood urate may be raised, and there is no rise in venous lactate with exercise testing.

In the UK, the reference says “hot spot” DNA testing for the two most common mutations can be arranged through the national McArdle service, and that up to 85% of patients can be confirmed without a muscle biopsy. Where biopsy is used it shows excess glycogen and absence of the muscle enzyme phosphorylase, and DNA testing then provides genetic confirmation.

Conditions that can look similar include other glycogen storage diseases and other causes of fatigue and exercise intolerance, which is one reason diagnosis can be delayed. UCLH lists McArdle disease alongside related conditions such as Tarui disease, glycogen storage disease type 9d, beta-enolase deficiency, glycogen synthase deficiency, rhabdomyolysis and RYR1 disorders among the conditions treated by its service.

There is no specific treatment. AGSD-UK says people with McArdle disease should take regular aerobic exercise such as walking and limit anaerobic activities such as lifting heavy weights to no more than 6 seconds at a time. Patient.info’s reference advises avoiding strenuous, anaerobic or sustained activity, including lifting or pushing, not continuing to exercise in the presence of pain, and taking regular gentle exercise such as walking or cycling, which it describes as the most effective way of controlling symptoms and improving quality of life.

It also advises avoiding excessive weight gain because extra weight lowers the aerobic threshold and increases the effort of exercise. It says that although there is some evidence of benefit with creatine, oral sucrose, ramipril and a carbohydrate-rich diet, there is no strong evidence of significant clinical benefit, and that there are some reports that vitamin B6 may be beneficial.

AGSD-UK rates the outlook as good with gentle aerobic exercise and only very brief anaerobic activity, and says that with diagnosis, correct advice can be followed and further problems avoided. Patient.info’s reference calls it a chronic but often relatively benign disorder, says progression to chronic kidney disease has not been described and that severe rhabdomyolysis may lead to acute kidney injury. It adds that there does not seem to be any adverse effect on pregnancy and childbirth, and that genetic counselling is appropriate.

The UCLH service describes a multidisciplinary team that includes consultant neurologists, a clinical nurse specialist, a neuromuscular physiotherapist, an exercise physiologist, a clinical psychologist, a clinical scientist and dietitians, with a dedicated paediatric clinic to provide continuity from childhood to adulthood. It works closely with AGSD-UK and the International Association for Muscle Glycogen Storage Disease.

UCLH says it accepts referrals nationwide for adults and children from GPs and hospital consultants. Most diagnosis and long-term advice for McArdle disease therefore runs through this NHS highly specialised service, with local care and your GP handling everyday matters.

Private neurology or physiotherapy can be used for second opinions or additional support, but it is sensible to make sure any exercise advice matches that of the national service, because exercise guidance in this condition is specific.