McArdle's disease
McArdle's disease, also known as glycogen storage disease type V, is a genetic disorder characterized by the inability to release glucose from glycogen during strenuous exercise due to a deficiency of the enzyme myophosphorylase. First described in 1951, this rare condition primarily affects men and is inherited in an autosomal recessive pattern. McArdle's disease typically presents symptoms like muscle weakness, cramping, pain, exercise intolerance, and fatigue, which can lead to serious complications such as myoglobinuria and rhabdomyolysis following intense physical activity. Diagnosis often involves muscle biopsy and various biochemical tests, but routine screening is not common unless there is a family history.
There is currently no definitive treatment for McArdle's disease; however, some management strategies include a high-protein, high-carbohydrate diet, vitamin B6 supplementation, and gradual aerobic conditioning to help prevent muscle damage. While individuals with McArdle's may live into old age, they can experience chronic muscle weakness and the potential for permanent muscle injury over time. Generally, understanding and managing the condition involves a collaborative approach that respects the individual experiences of those affected.
McArdle's disease
ALSO KNOWN AS: McArdle disease; glycogen storage disease type V; muscle phosphorylase deficiency
DEFINITION McArdle’s disease was first described in 1951 by British pediatrician Brian McArdle. It is among the most common of the glycogen storage deficiency diseases. With strenuous exercise, there is the inability to release glucose for energy from glycogen due to lack of the enzyme myophosphorylase.
Risk Factors
McArdle’s disease is caused by autosomal recessive inheritance of two copies of a defective gene on chromosome 11q13. It is more common in men. Although it is usually present from birth, McArdle’s disease is typically diagnosed in the early adult years. It is a rare condition. In 2023, researchers estimated that it occurs in 1 in 50,000 to 1 in 200,000 people in the United States.
Etiology and Genetics
According to 2023 information from the National Library of Medicine, about 179 mutations of the PGYM gene, on chromosome 11q12–13, were related to McArdle’s disease. This could account for the variation in the severity and scope of the symptoms of this condition. There is no clear genotype-phenotype correlation. One of the most common mutations is at 50 and is called the R50X mutation. This mutation prematurely ends myophosphorylase production. It was found in 81 percent of cases of McArdle’s disease in the United Kingdom, 63 percent in the United States, and 50 percent in continental Europe. Other mutations interfere with myophosphorylase production by the replacement of a base with the incorrect base. A specific series of bases is required to produce myophosphorylase.
Myophosphorylase is an that is an essential element of the Krebs cycle, which produces energy in the form of ATP (adenosine triphosphate) for muscular action. While muscles contain small amounts of sugar that are adequate for normal activity, when strenuous activity or anaerobic activity is attempted, the muscles quickly run out of energy and then are unable to function.
If strenuous activity is begun slowly, then the muscles convert to using the breakdown of free proteins and fatty acids for energy. This shift in energy source provides a so-called second wind that permits the continuation of exercise. This does not occur with isometric or other anaerobic activities.
Symptoms
The symptoms of muscle weakness, cramping, pain, exercise intolerance, and fatigue are caused by the lack of energy for the muscles. Myoglobinuria and rhabodomyolysis are symptoms of damage to muscle tissue from strenuous or anaerobic exercise. Myoglobinuria is caused by rhabodomyolysis, which is the destruction of muscle tissue leading to the release of large protein molecules. These molecules contain iron-bearing tissue, which causes the dark red-brown color of the urine. The large size of the muscle cells can lead to acute kidney failure by clogging the nephrons of the kidneys.
Screening and Diagnosis
McArdle’s disease is not routinely screened for, unless there is a family history of this condition. It is diagnosed by muscle biopsy, serum creatine levels, serum lactic acid levels, phosphorus 31-nuclear magnetic resonance imaging, electromyography (EMG), and the ischemic arm test.
Muscle biopsy is the removal of a small amount of muscle tissue for gross and microscopic examination. Gross examination demonstrates a moth-eaten look to muscles. These apparent “holes” in the muscle are actually deposits of glycogen. Muscle tissue may have abnormally large cells or large numbers of cells. There may be abnormal splitting of muscle fibers, and there may be areas of muscle necrosis (death). Microscopic examination includes the evaluation of myophosphorylase activity in the muscles and of the genetic material of the muscle cells.
Serum creatine kinase (CK) is elevated in McArdle’s disease. It is a breakdown product of damaged muscle. Serum lactic acid is abnormally decreased or absent. Lactic acid is produced during exercise. Phosphorus 31-nuclear magnetic resonance is the use of a radioactive dye, phosphorus 31, with magnetic resonance imaging. This dye demonstrates the lack of lactic acid in muscle during exercise. Electromyography is the stimulation of specific muscles with low levels of electricity. In patients with McArdle’s disease, EMG demonstrates some muscle irritability but otherwise is normal.
The ischemic arm test creates artificial muscle ischemia with a blood pressure cuff. Then, serum samples of lactic acid and ammonia are tested. Normally both the lactic acid and ammonia increase, but in McArdle’s disease, the lactic acid and ammonia do not change.
Treatment and Therapy
There is no real treatment for McArdle’s disease. There are treatment theories, but these theories do not work for everyone. The most prevalent theory is a high-protein, high-carbohydrate diet, which provides substances that are easily converted to glucose. High-sucrose drinks or sugary food before strenuous exercise can prevent loss of muscle function in some persons. Vitamin B6 (pyridoxine) supplementation is often helpful with McArdle’s. A large percentage of B6 in the body is bound to myophosphorylase. Aerobic conditioning that is gradually increased can prevent muscle damage.
Prevention and Outcomes
There is no way to prevent McArdle’s disease. The best outcomes are achieved by preventing muscle injury. Most persons with McArdle’s disease may survive to old age, when they may develop chronic muscle weakness and permanent muscle damage.
Bibliography
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Lucia, Alejandro, et al. “McArdle Disease: What Do Neurologists Need to Know?” Nature Clinical Practice Neurology 4 (2008): 568–77. Print.
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