$Unique_ID{BRK03978} $Pretitle{} $Title{McArdle Disease} $Subject{McArdle Disease Glycogenosis Type V Glycogen Storage Disease Type V Myophosphorylase Deficiency Forbes Disease Pompe Disease Tarui Disease } $Volume{} $Log{} Copyright (C) 1987, 1989, 1992 National Organization for Rare Disorders, Inc. 395: McArdle Disease ** IMPORTANT ** It is possible the main title of the article (McArdle Disease) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Glycogenosis Type V Glycogen Storage Disease Type V Myophosphorylase Deficiency Information on the following diseases can be found in the Related Disorders section of this report: Forbes Disease Pompe Disease Tarui Disease General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. McArdle Disease is a glycogen storage disease. Symptoms of this hereditary metabolic disorder are caused by an inborn lack of the enzyme myophosphorylase. This enzyme is needed for the breakdown of glycogen (the body's form of stored energy) into sugar (glucose) in muscle tissues. In McArdle Disease the breakdown of glucose cannot take place. Severe muscle cramps occur as a result of heavy exercise. Symptoms Diagnosis of McArdle Disease usually does not occur before 10 years of age due to the relatively mild course of the disorder. Children with McArdle Disease usually develop normally. Muscles usually function normally while at rest or during moderate exercise. Only during strenuous exercise do severe muscle cramps occur, usually during late childhood or adolescence. Myoglobin (released during muscle breakdown) can often be detected in urine after strenuous exercise. In severe cases kidney failure may occur if the condition is not treated promptly. The biomedical literature suggests that an abnormality in oxygen transport to the skeletal muscles may also be present in individuals with McArdle Disease. Causes McArdle Disease is an autosomal recessive genetic disorder. It is caused by a lack of the enzyme myophosphorylase. This enzyme is needed for the breakdown of stored energy (glycogen) into sugar (glucose). The lack of sugar during strenuous exercise causes the severe muscle cramps of McArdle Disease. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal.) Affected Population All Glycogen Storage Diseases together affect less than 1 in 40,000 persons in the United States. Females and males are affected in equal numbers. Related Disorders Glycogen Storage Diseases are caused by inborn errors of metabolism in which the balance between stored energy (glycogen) and available energy (sugar or glucose) is disturbed. Too much glycogen tends to be stored in the liver and muscles and too little sugar is available in the blood. The following diseases are similar to McArdle Disease. These can be compared to McArdle Disease for a differential diagnosis: Pompe Disease is a hereditary glycogen storage disease. This hereditary metabolic disorder is caused by a lack of the enzyme alpha-1,4 glucosidase (lysosomal glucosidase; acid maltase). In this disorder, glycogen tends to accumulate in all body tissues, especially in the heart muscle. Forbes Disease (Glycogenosis III; Cori Disease) is another glycogen storage disease inherited through autosomal recessive genes. Symptoms are caused by a lack of a debrancher (amylo-1,6 glucosidase) enzyme. This enzyme deficiency causes excess amounts of glycogen derived from carbohydrates to be deposited in the liver, muscles, and heart. The nerves in the back of the legs and on the sides of the heel and foot (sural nerves) also tend to accumulate excess glycogen. The heart may be involved in some cases. Tarui Disease (Phosphofructokinase Deficiency) is another type of glycogen storage disease. Symptoms of this genetic metabolic disorder are caused by an inborn lack of the enzyme fructophosphokinase in muscle, and a partial deficiency of this enzyme in red blood cells. The deficiency prevents the breakdown of glucose into energy. Tarui Disease is characterized by pain and muscle cramps during muscle stress, but often to a less severe degree than in McArdle Disease. For more information on the above disorders, choose "Pompe," "Forbes," and "Tarui" as your search terms in the Rare Disease Database. Therapies: Standard Diagnosis of McArdle Disease is made from a history of painful muscle cramps during exercise, and from functional testing. Demonstration of a lack of the enzyme muscle phosphorylase (myophosphorylase) confirms the diagnosis. The functional testing consists of a muscle exercise test with blood supply reduced using a blood pressure cuff. A failure to see a rise in the blood lactate, one of the normal breakdown products of glucose in muscle, confirms the diagnosis of McArdle Disease. A muscle biopsy (withdrawal of a very small part of a live muscle through a needle), is performed and tested for myophosphorylase enzyme. Phosphorylase activity will be lacking or absent in the muscles of a patient with McArdle Disease. Treatment usually consists of the avoidance of strenuous exercise. Variable results have been obtained with oral glucose and fructose treatment. For women with McArdle Disease who need a Caesarean section during delivery, special consideration should be given to appropriate anesthesia. Therapies: Investigational Dr. Y.T. Chen at Duke University Medical Center, at the request of the Glycogen Storage Disease Association, is collecting DNA from patients with Glycogen Storage Disease Type I to form a DNA bank for GSDI. Interested patients may contact the Glycogen Storage Diseases Association for further information. The address and phone number of the organization are listed in the Resources section of this report. Clinical trials are underway to study the role of NH3 in ventilary control during exercise. Interested persons may wish to contact: David M. Systrom, M.D. Pulmonary & Critical Care Unit Massachusetts General Hospital Boston, MA 02114 (617) 726-3734 to see if further patients are needed for this research. This disease entry is based upon medical information available through January 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on McArdle Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Association for Glycogen Storage Diseases Box 896 Durant, IA 52747 (319) 785-6038 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For genetic information and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References CECIL TEXTBOOK OF MEDICINE, 18th ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Eds.: W.B. Saunders Co., 1988. Pp. 1135. THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. Pp. 2078.