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What is McArdle's disease?McArdle's disease is a metabolic muscle disorder first described in1951 by Dr Brian McArdle. The disorder is also called Glycogen StorageDisease Type V (GSD V). People born with McArdle's disease are unableto produce an enzyme called muscle phosphorylase. This enzyme isimportant in producing the fuel source required by the skeletal musclesfor exercise.
What are the symptoms?People with McArdle's disease develop severe muscle pain and fatiguein the first few minutes of exercise. If exercise is continued despitethe pain, a severe muscle spasm or contracture will develop. Thisresults in muscle damage leading to myoglobinuria, a darkdiscolouration of the urine.
Many people with the condition remember painful symptoms from earlychildhood but the disorder is rarely diagnosed before adulthood. Somepeople notice a worsening of their symptoms in middle-age and this maybe accompanied by some muscle wasting, especially over the shouldersand back. Most people live normal lives and learn to improve theirexercise tolerance using a "second wind".
What is a second wind?There are two types of exercise: aerobic exercise includes walking,gentle swimming, jogging and cycling. Anaerobic exercise is moreintense or sustained exercise and includes running, walking uphill andcarrying loads. The first few minutes of any exercise are usuallyanaerobic.
Normally, during anaerobic exercise, muscle phosphorylase convertsglycogen (stored starch) to glucose (sugar). The glucose enters ametabolic pathway known as the glycolytic pathway, which ultimatelyproduces ATP (energy). During aerobic exercise, the main energy sourcecomes from free fatty acids carried in the blood stream. These fattyacids enter a different metabolic pathway, called oxidativephosphorylation, which takes place in the mitochondria (these are thepower houses of the cell) the end result is the production of ATP(energy).
A second wind is like a key opening the door, enabling exercisewithout pain for people with McArdle's disease. After a few minutes ofexercise when pain occurs, if the individual rests for a moment or two,exercise can be continued without severe pain. The second wind probablyresults from a switch in metabolic pathway from the glycolytic pathwayto oxidative phosphorylation.
Which muscles are affected?Any skeletal muscle is affected. Usually walking brings on symptomsin the legs and carrying heavy shopping affects the arms. Sawing,digging or squatting may affect the back muscles and some peopledevelop pain eating chewy foods.
How is McArdle's disease diagnosed?A blood test will usually reveal a raised muscle enzyme known ascreatine kinase (CK). Sometimes a forearm lactate test is performed,although this is not essential. The diagnosis is confirmed by a musclebiopsy, which shows an excess of glycogen and absence of the muscleenzyme phosphorylase. In up to 85% of patients from Northern Europe, anabnormality in the gene encoding for muscle phosphorylase, called R50X(previously known as R49X), can be detected on a DNA test (blood test).In practice such testing is rarely helpful and not always available andis not essential to make the diagnosis.
Is there any treatment?The ability to develop a second wind is greatly increased by keepingphysically fit. Taking regular gentle aerobic exercise, such as walkingis important. At the start of exercise, when pain occurs, slow rightdown or stop until the pain has subsided, then try again. Sustained orsevere exercise, such as weight lifting, or sprinting, must be avoidedbecause of the high risk of muscle damage. Continuing to exercise inthe presence of severe pain will also result in muscle damage andmyoglobinuria, which will in turn increase the risk of acute renalfailure.
Many different diets and supplements have been tested in McArdle'sdisease such as high protein diet, vitamin B6 and creatine supplements,as yet there is insufficient evidence to suggest that any of thesebenefit people with McArdle's disease. There is some evidence tosuggest that a sugary drink prior to planned exercise might help. Thishowever, needs to be balanced against excessive weight gain, whichshould be avoided at all cost. Carrying increased weight will loweryour body's aerobic threshold and make exercise more difficult. Keeping aerobically fit is the best way to condition McArdle's musclesto improve performance and improve quality of life.
What happens if myoglobinuria occurs?Most people with McArdle's disease will develop myoglobinuria atsome time in their lives. Myoglobinuria is a dark discolouration of theurine from a red- brown colour (mild) to a brown-black colour (severe).This is a warning sign for acute renal failure, which can occur ifsevere muscle damage has occurred. If this happens the kidneys stopproducing urine because the draining tubules become blocked with theproducts of muscle breakdown.
If the episode of pain and contracture was not too severemyoglobinuria will be transient and lighter in colour. After moresevere episodes the muscles may be swollen and tender and there may beflu like symptoms. Minor symptoms are managed by increasing fluidintake to maintain a good urine output. More severe episodes willrequire an admission to hospital for intravenous fluids and if kidneyfailure occurs, a period of dialysis may be required. Kidney failure isalmost always reversible, but expert treatment is required immediatelyto prevent complications during the acute stage. It is, therefore, veryimportant to seek medical help early should any of these symptoms occur.
Are there any other precautions?There is a reported risk of acute muscle damage, with certaingeneral anaesthetics (usually muscle relaxants and inhaledanaesthetics), although in practice problems appear to be very rare.The anaesthetist should be made aware of the diagnosis of McArdle'sdisease, and may choose to avoid certain anaesthetic agents.Tourniquets should not be used during operative procedures in patientswith McArdle's disease.
Affected women do not seem to be disadvantaged by pregnancy orchildbirth. A natural childbirth is a realistic possibility for womenwith McArdle's disease.
Will I become disabled?McArdle's disease does not affect life expectancy. Some people donotice a slow deterioration in their symptoms over many years but byfar the majority of people remain independent and able to walk.
Can it be passed on to my children?The condition is caused by a recessive gene. This means that oneabnormal copy of the gene is passed from each parent to the affectedchild, who in turn will have inherited two abnormal copies of the gene.The risk for both carrier parents to have an affected child is 1:4 foreach pregnancy.
People who have McArdle's disease do not usually pass the conditiononto their own children because one normal copy of the gene will havebeen provided by their partner. However, all of their children will becarriers. Generally speaking carriers do not have symptoms.