McArdle disease

This is part of Rare diseases.

Diagnosis: McArdle disease

Synonyms: Glycogenosis type V, Myophosphorylase deficiency


Date of publication: 2006-10-30
Version: 1.2

The disease

McArdle’s disease, also known as myophosphorylase deficiency, is caused by a deficiency of phosphorylase in muscle tissue (myo = muscle). Phosphorylase plays a vital role in the breakdown of glycogen, a polysaccharide found primarily in the liver and muscles. Another name for the condition is glycogenosis type V, referring to the abnormal glycogen accumulation in muscle tissue. Normally, phosphorylase converts stored glycogen into glucose, which is the main energy source for intensive muscle work. In the absence of glucose, exercise will trigger pain and muscle weakness in individuals with McArdle’s disease.

In 1951, English neurologist Brian McArdle published the first case report describing a patient in whom physical activity generated pain, weakness and muscle stiffness. All muscle groups were involved, including the muscles used for chewing. The symptoms were instantly relieved when activity ceased. McArdle also observed that the normal rise in blood lactic acid levels during exercise failed to present.

McArdle’s disease is one of several glycogen metabolic disorders. The Swedish rare disease database also contains information about Pompe’s disease and Tarui’s disease, all belonging to this group.


There is currently no reliable data about the frequency of McArdle’s disease. American studies estimate a prevalence of approximately 10 cases per million population. In Sweden the disease occurs even less frequently. The disorder is more common in men than in women.


The enzyme phosphorylase is needed to catalyse reactions converting stored glycogen to glucose, the main energy source for anaerobic muscle work. Muscle work performed at an intensity of more than 50 per cent of maximal oxygen consumption is mainly anaerobic, i.e. oxygen is not used.

In McArdle’s disease patients, because they lack the enzyme needed to perform the conversion to glucose, glycogen accumulates in muscle tissue. Alternative fuel sources include energy-rich phosphates (adenosine triphosphate and phosphocreatine) and fat. The problem is that phosphates only supply energy for short-duration muscle work (up to 30 seconds), and fat is used mainly in low-intensive exercise and at rest. However, with regular, gentle aerobic exercise it is possible to boost one’s capacity to use energy from fat in moderate exercise.

Exercise intensity should always remain moderate, as sustained, intensive muscle work may result in a muscle-cell energy crisis and subsequent muscle-cell degeneration.

Damaged muscle cells may leak a number of substances into the bloodstream, including electrolytes such as potassium, enzymes such as phosphocreatine, and myoglobin, a red muscle pigment that can cause kidney damage in high concentrations.

In rare cases, the affected person only has partial myophosphorylase deficiency, and the symptoms may be milder.

The gene coding for the enzyme myophosphorylase is located on chromosome 11 (11q13), and is known as PYGM. Two mutations in this gene explain more than 50 per cent of all cases of McArdle’s disease, but several other PYGM mutations also cause complete or partial myophosphorylase deficiency.


McArdle’s disease is a hereditary autosomal recessive disorder. This means that both the parents of a child with the syndrome are healthy carriers of the mutated gene. In each pregnancy where both parents are healthy carriers there is a 25 per cent risk that the child will inherit the disease. In 25 per cent of the cases the child will neither inherit the disease nor be a carrier of the mutated gene. In 50 per cent of the cases the child will inherit one recessive mutant gene and, like the parents, he or she will be a healthy carrier.

Autosomal recessive inheritance of genetic traits

If one parent is not a carrier, but the other has an inherited autosomal recessive disorder (and thus has two defective genes), the children will all be carriers of the defective gene but the condition will not affect them. If an individual with an inherited autosomal recessive disorder has a child with someone who has one copy of the defective gene, there is a 50 per cent risk that the child will develop the condition, while in 50 per cent of the cases the child will be a healthy carrier.


Symptoms usually present in childhood, before puberty. Fatigue is often the first sign of the disease, followed by painful muscle contractions. Sometimes the diagnosis is not established until adulthood, following a period of slow progressive muscle weakness.

Symptoms arise when muscles are not supplied with sufficient energy. Straining activities, such as running, walking, carrying or lifting heavy loads trigger a muscle-cell energy crisis causing pain, cramping, weakness and muscle stiffness. Symptoms are sometimes alleviated if moderate activity is sustained (“second wind” phenomenon). This happens because blood circulation increases gradually, allowing energy from liver glucose and fatty acids to reach the mitochondria, the cell “energy plants”. As a result, muscles are able to work more effectively. Complete symptom relief is achieved by resting.

Rapid heart beat, breathlessness and nausea are other symptoms that may present during anaerobic exercise.

Myoglobulinuria is a serious complication that affects 50 per cent of all persons with McArdles’s disease and requires acute hospital care. The condition results when myoglobin leaks into the blood from muscle cells. The pigment may precipitate in the kidneys, producing a reddish urine discoloration. Approximately 25 per cent of individuals affected by myoglobulinuria develop acute renal failure requiring dialysis therapy.

Elevated blood potassium concentrations may affect heart function.

High serum phosphocreatine levels may be a warning sign of muscle fibre damage. In approximately one third of affected individuals, recurring episodes of muscle fibre damage result in mild chronic muscle weakness.


The diagnosis is established using a number of tests:

  • A forearm exercise test is an important diagnostic tool for detecting abnormalities in muscle carbohydrate metabolism. The patient is asked to alternately contract and extend the hand for one minute, and blood samples for measuring lactate and ammonia concentrations are drawn before and after the test. In a healthy patient lactate levels will have tripled after the test, and return to normal within 10 minutes. In a person with McArdle’s disease lactate levels fail to rise, but the blood ammonium concentration will be elevated.
  • A bicycle exercise test will show a characteristic decrease in heart rate after approximately 10 minutes of cycling.
  • An electromyogram (EMG) test is used to measure the electrical activity of muscles under ischaemic conditions (without oxygen).
  • Histochemical tests are used to localise various cell substances. The diagnosis is confirmed by chemical analysis of a muscle biopsy (a small sample of muscle tissue), which will detect the absence of phosphorylase. Phosphorylase analysis is carried out in the Netherlands (see under “Resources” heading).

Prenatal diagnosis is possible. DNA-based diagnostics is usually possible. Genetic counselling should be offered as soon as the diagnosis is established.


There is no cure for McArdle’s disease, but various treatments may alleviate the symptoms.

Individuals with McArdle’s disease should be observant for myoglobulinuria, presenting as a dark discolouration of the urine. Due to the risk of kidney damage, medical help should be sought immediately if symptoms arise. Dialysis therapy is needed if toxic waste products accumulate in the urine (uraemia), owing to renal failure.

The disease is associated with a slightly elevated risk of muscle damage related to anaesthesia. The anaesthetist must therefore be informed about the condition prior to any surgical intervention.

Diet management has been shown to have some effect on the provision of energy for muscle work. Carbohydrate intake should be high enough to maintain a high level of liver glycogen, ensuring a relatively high glucose concentration in the blood. Intake of sucrose before muscular activity enhances performance.

Creatine supplementation may boost short term muscle strength and the ability to perform short-duration, high-intensity activities. Dietary management should be supported by a dietician.

Although high-intensive muscle work such as weight lifting should be avoided, physical activity in general is important for maintaining physical and mental health. Physical activity should be preceded by careful warm-up exercises in order to increase muscular blood flow. Regular gentle exercise at an intensity of approximately 50 per cent of maximal oxygen uptake is recommended (20-40 minutes, 3-4 times per week). A physiotherapist is able to provide advice and will help design a suitable exercise programme.

Individuals with McArdle’s disease can usually carry out household work and jobs not requiring strenuous muscle effort, although all activities must be adapted to the limitations and capacities of the individual. Depending on the severity of the disorder, routines may have to be modified in order to facilitate daily life activities in the home, at school and the workplace. Various aids may also be useful. An occupational therapist should be contacted for advice and practical assistance.

Preschool and school staff should be informed about the condition as physical activities must be adapted to suit the child. Contact with a paediatric treatment and training centre should be established early, as these facilities offer the coordinated services of professionals from a wide range of fields, for example occupational therapists, guidance counsellors, physicians, psychologists and physiotherapists, all working to optimise the child’s capacities.

With the exception of having to avoid intensive muscle work, most people with the disease live normal lives and the need for treatment is highly individual. Once the causes of the condition and preventive measures have been explained, it may be easier to make choices about education and suitable career paths as well as what types of games and sports to participate in.

If the diagnosis is confirmed and information about the condition has been provided, follow-up examinations are usually not required. Medical help should be sought if new symptoms such as permanent muscle weakness arise.

Practical advice


National and regional resources in Sweden

Investigations of suspected cases of McArdle’s disease are carried out in units specialising in neuromuscular disorders.

Phosphorylase analyses are carried out in the Netherlands. Contact person: Dr O P van Diggelen, Department of Clinical Genetics, Erasmus MC, Ee 2402, University Medical Centre Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands. Tel +31-10-408 7224, fax +31-10-408 7200, email: vandiggelen@kgen.fgg.eur.nl.

Resource personnel

Björn Lindvall, Senior physician, Department of Neurology, Örebro University Hospital, SE-701 85 Örebro, Sweden. Tel +46 19 602 10 00, email: bjorn.lindvall@orebroll.se

Associate Professor Göran Solders, Department of Neurology, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. Tel +46 8 585 800 00, email: goran.solders@karolinska.se

Courses, exchanges of experience, recreation


Organizations for the disabled/patient associations

The Scandinavian Association for Glycogen Storage Disease, SAGSD, was founded in Sweden and is a Scandinavian network for people with glycogen storage diseases and their relatives. Contact Marcus Landgren, postmaster@sagsd.org, www.sagsd.org.

NHR, The Swedish Association of Persons with Neurological Disabilities. Visiting address: S:t Eriksgatan 44, Stockholm. Mailing address: Box 490 84, SE-100 28 Stockholm. Tel +46 8 677 70 10, fax +46 8 24 13 15, email: nhr@nhr.sewww.nhr.se.

RBU, The Swedish National Association for Disabled Children and Young People. Visiting address: S:t Eriksgatan 44, Stockholm. Mailing address: Box 8026, SE-104 20 Stockholm, Sweden. Tel +46 8 677 73 00, Fax +46 8 677 73 09, email: info@riks.rbu.sewww.rbu.se.

Rare Diseases Sweden is a federation of rare disease organizations, serving the interests of people with rare disorders.

Rare Diseases Sweden. Street address: Sturegatan 4A, Sundbyberg. Mailing address: Box 1386, SE-172 27 Sundbyberg, Sweden. Tel +46 8 764 49 99,
email: info@sallsyntadiagnoser.sewww.sallsyntadiagnoser.se.

Courses, exchanges of experience for personnel


Research and development (R&D)

Treatment trials with genetically engineered phosphorylase are ongoing.

Information material

An information booklet on McArdle’s disease, which summarises the information in this database text, is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2003-12-167). Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.


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DiMauro S, Lamperti C. Muscle glycogenoses. Muscle Nerve 2001; 24: 984-999.

el-Schahawi M, Tsujino S, Shanske S, DiMauro S. Diagnosis of McArdle’s disease by molecular genetic analysis of blood. Neurology 1996; 47: 579-580.

Flodmark B, Ockander L. Misstänk McArdles sjukdom vid muskelsmärta. Läkartidningen 1995; 92: 2020-2022.

Haller RG. Treatment of McArdle disease. Arch Neurol 2000; 57(7): 923-924.

Haller RG, MacLean D, Vissing S, Vissing J. Aerobic conditioning: an effective therapy in McArdle’s disease. Neurology 1998; 50: A 369.

Kazemi-Esfarjani P, Skomorowska E, Jensen TD, Haller RG, Vissing J. A nonischemic forearm exercise test for McArdle disease. Ann Neurol 2002; 52: 153-159.

Martin MA, Rubio JC, Buchbinder J, Fernandez-Hojas R, del Hoyo P, Teijera S et al. Molecular heterogenity of myophosphorylase deficiency (McArdle’s disease): a genotype-phenotype correlation study. Ann Neurol 2001; 50: 574-581.

McArdle B. Myopathy due to a defect of muscle glycogen breakdown. Clin Sci 1951; 10: 13-33.

Ollivier K, Hogrel JY, Gomez-Merino D, Romero NB, Laforet P, Eymard B et al. Exercise tolerance and daily life in McArdle’s disease. Muscle Nerve 2005; 31: 637-641.

Pari G, Crerar MM, Nalbantoglu J, Shoubridge E, Jani A, Tsujino S et al. Myophosphorylase gene transfer in McArdle’s disease myoblasts in vitro. Neurology 1999; 12: 1352-1354.

Quinlivan R, Beynon RJ. Pharmacological and nutritional treatment for McArdle’s disease (Glycogen Storage Disease type V). Cochrane Database Syst Rev 2004: CD003458.

Vissing J, Haller RG. A diagnostic cycle test for McArdle’s disease. Ann Neurol 2003; 54: 539-542.

Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle’s disease. N Engl J Med 2003; 349: 2503-2509.

Vorgerd M, Zange J, Kley R, Grehl T, Husing A, Jager M et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Arch Neurol 2002; 59: 97-101.

Database references

OMIM (Online Mendelian Inheritance in Man).
Internet: www.ncbi.nlm.nih.gov/omim
search: mcardle disease, glycogen storage disease V

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical experts who wrote the draft of this information material are Professor Arne Lundblad and Associate Professor Karl-Gösta Henriksson, Linköping University Hospital, and Associate Professor Göran Solders, Karolinska University Hospital, Sweden.

The revision was carried out by Associate Professor Göran Solders, Karolinska University Hospital, Sweden.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

The expert group on rare diseases of the Swedish National Board of Health and Welfare approved the material prior to publication.

Date of publication: 2006-10-30
Publication date of the original Swedish version: 2006-06-26

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden, tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.


About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.