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More about McArdle Disease

 
This page was written by
Dr Ros Quinlivan FRCPCH FRCP, Neuromuscular Physician,


Introduction
 
McArdle disease is a rare metabolic muscle disorder, first described in 1951. The disorder is also known as Glycogen Storage Disease Type V or Myophosphorylase Deficiency. Individuals born with McArdle disease are unable to produce an enzyme known as myophosphorylase, which is important for creating a fuel source for exercise.
 
There are two types of exercise: 
1. Aerobic exercise, such as: jogging, cycling and walking. 
2. Anaerobic/sustained exercise, such as: sprinting, carrying heavy loads, weight lifting and walking uphill.
 
Normally, during anaerobic exercise, myophosphorylase converts glycogen to glucose within the muscle. This, in turn, following a series of metabolic stages, is converted to lactate and then energy in the form of Adenosine Triphosphate (ATP). 
 
During aerobic exercise, the main energy source comes from free fatty acids, which are converted to ATP following a series of reactions in the mitochondria. The mitochondria are the "power houses" of the cell, producing energy. 
 


Symptoms
 
People with McArdle disease experience symptoms during anaerobic and sustained exercise. These include fatigue and then pain occurring within a few minutes of exercise, which if continued, leads to muscle spasm known as a contracture. Following severe exercise, muscle damage may occur leading to myoglobinuria. This is a dark discolouration of the urine and may be a warning sign for acute renal failure, which results from excessive muscle breakdown. 
 
The symptoms may frequently be present from early childhood, although the disorder is rarely diagnosed before the second or third decade. Many people notice a worsening of the symptoms with age, particularly in middle-age, when muscle wasting may also be seen. 
 
Fatigue is a dominant symptom for some patients, which may be misdiagnosed as having chronic fatigue syndrome. 
 
There does seem to be tremendous variability between individuals in terms of the severity of their symptoms. Some people manage normal activity including sport, while others are moderately restricted in terms of their physical ability. 
 


Diagnosis
 
A simple blood test will usually reveal a raised muscle enzyme called the creatine kinase (or CK). Some doctors will perform an exercise lactate test, however, this test is not diagnostic for McArdle disease and can be unpleasant. The diagnosis is confirmed by muscle biopsy, which shows an excess of glycogen and absence of muscle phosphorylase. In up to 85% of patients from Northern Europe, an abnormality in the gene encoding for muscle phosphorylase, called the R50X mutation, can be detected on a blood test. 
 


Genetics
 
McArdle disease is inherited in an autosomal recessive fashion. This means that both parents must be carriers. One abnormal copy of the gene is passed from each parent to the affected child, who, in turn, will have inherited two abnormal copies of the gene. The risk of two carrier parents producing an affected child is 25% (1 in 4) for each pregnancy.
 
Individuals known to have McArdle disease, usually, do not pass the disorder on to their own children, since one normal copy of the gene will be provided by their partner. However, all of their children will be carriers. Generally speaking, carriers do not have symptoms. 
 


Management
 
It is important to avoid strenuous (anaerobic) exercise including lifting or pushing. If an episode of myoglobinuria occurs, drink plenty of fluids, if you feel unwell or stop producing urine, seek medical attention immediately. (See the emergencies page.)
 
It is important to take regular gentle exercise, such as walking or cycling. Keeping your body physically fit is the most effective way of controlling the symptoms of McArdle disease and improving your quality of life. Although muscles cannot use stored glycogen, they can use glucose and fat as fuels for exercise. The switch to these fuel sources enables people with McArdle disease to enter a "second wind", a period of effective less painful exercise after the initial period of cramping.
 
The ability to switch to these alternative fuel sources is greatly increased if individuals keep themselves fit by undertaking regular aerobic exercise. At the start of exercise, when pain occurs, slow right down or stop until the pain subsides (usually just for 30 seconds), then try again. Continuing to exercise with intense pain will result in muscle damage and should be avoided.
 
For severe pain, following an episode of excessive exercise, analgesics may be required, however, drugs are not the ideal method for treating daily pain. Prevention of pain by carefully pacing exercise if the best strategy.
 
Eat a sensible balanced diet. Many different diets have been advocated (e.g. high protein diet, high carbohydrate) however, there is as yet no good evidence that any particular diet helps to reduce symptoms. Vitamin supplementation has not been shown to benefit patients. 
 
Avoiding excessive weight gain is important, as increased weight lowers the aerobic threshold and increases the effort of exercise. Furthermore, dieting reduces the availability of certain energy sources. 
 
Should an anaesthetic be required, it is important that the anaesthetist be informed as there is a small risk of muscle breakdown (rhabdomyolysis) with certain anaesthetics. If the anaesthetist is made aware, appropriate precautions can be taken. Tourniquets should not be used during operative procedures. 
 
Affected women do not seem to be disadvantaged by pregnancy or childbirth. A normal childbirth is possible in women with McArdle's disease.