Glycogen Storage Disease Type V

National Organization for Rare Disorders, Inc.

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  • Glycogen Storage Disease Type V
  • Glycogenosis Type V
  • Myophosphorylase Deficiency
  • GSD V
  • Glycogen Storage Disease
  • McArdle Disease

Disorder Subdivisions

  • None

General Discussion

Glycogen storage disease type V (McArdle Disease or GSD-V) is one of several inherited glycogen storage diseases all of which are caused by failures of specific enzymes required for the storage of energy-supplying glycogen. In the case of GSD-V, symptoms are caused by the lack of the crucial enzyme muscle phosphorylase (myophosphorylase). This enzyme is needed for the breakdown of glycogen (the body's form of stored energy) into sugar (glucose) in muscle tissues. All of the glycogen storage diseases are characterized by the inability to break down glycogen, but in each case this occurs for a different reason. Unlike most of the other GSDs, type V has two autosomal recessive forms, a childhood-onset form and an adult-onset form. In addition, there is a much more rare autosomal dominant form of GSD-V. The clinical features of GSD-V are exercise intolerance, muscle cramping, and dark, burgundy-colored urine due to the presence of myoglobin (myoglobinuria).


Symptoms of childhood-onset glycogen storage disease type V usually present at about age 10, and in most cases the course of the disorder is relatively mild. Children with GSD-V 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. A characteristic feature of GSD-V is weakness accompanying strenuous exertion (exercise intolerance). Myoglobin, a protein 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.

Some individuals with GSD-V will, while exercising and after exhibiting signs of exercise intolerance, develop a second wind that allows them to continue exercising for a significant additional time without pain and cramping.

The literature suggests that an abnormality in oxygen transport to the skeletal muscles may also be present in individuals with glycogen storage disease Type V.

There have been reports of an extremely rare, usually fatal, neonatal form of the disorder as well as an equally rare, very late-onset form that presents at age 60 years plus.


In most cases, glycogen storage disease type V is an autosomal recessive genetic disorder, the responsible gene for which has been tracked to Gene Map Locus 11q13. With far less frequency, it can be inherited as an autosomal dominant disorder and there are cases in which it is caused by random gene mutations (sporadic inheritance).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 11q13" refers to band 13 on the long arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait which are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

GSD-V is very rare with only a few hundred cases reported in the literature. Some researchers believe that it is probably under-diagnosed because of the mildness of the symptoms. The neonatal, early-onset and very late-onset forms are even rarer. The classic form of GSD-V presents usually in early adolescence.

Standard Therapies


Glycogen storage disease Type V is diagnosed through the detailed history, exercise tolerance testing, and functional testing. Testing methods that avoid muscle biopsy are preferred and will likely include a muscle exercise test with blood supply reduced using a blood pressure cuff (ischemic forearm test) and electrical testing of the muscles and muscle fibers (electromyography). However, laboratory analysis to determine the presence of creatinine kinase as well as the lack of muscle phosphorylase (myophosphorylase) may be performed as well, and this requires biopsy material. A failure to see a rise in the blood lactate, one of the normal breakdown products of glucose in muscle, confirms the diagnosis.


Avoidance of strenuous exercise and taking vitamin B-6 often reduces muscle pain and cramping. Variable results have been obtained with oral glucose and fructose treatment. Aerobic exercise may improve exercise tolerance.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010


For information about clinical trials sponsored by private sources, contact:



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Chen Y-T. Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:1521-51.

Greene HL. Glycogen Storage Diseases. In: Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996.


Hadjigeorgiou GM, Sadeh M, Musumeci O, et al. Two novel mutations in the myophosphorylase gene in a patient with McArdle disease. Neuromuscul Disord. 2002;12:824-27.

Haller RG, Vissing J. Spontaneous "second wind" and glucose-induced "second wind" in McArdle disease: oxidative mechanisms. Arch Neurol. 2002;59:1395-402.

Kazemi-Esfarjani P, Skomorowska E, Jensen TD, et al. A non-ischemic forearm exercise test for McArdle disease. Ann Neurol. 2002;52:153-59.

Jensen TD, Kazemi-Esfarjani P, Skomorowska E, et al. A forearm exercise screening test for mitochondrial myopathy. Neurology. 2002;58:1533-38.

Vorgerd M, Zange J, Kley R, 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.

Martinuzzi A, Schievano G, Nascimbeni A, et al. McArdle's disease. The unsolved mystery of the reappearing enzyme. Am J Pathol. 1999;154:1893-97.

DiMauro S, Bruno C. Glycogen storage diseases of muscle. Curr Opin Neurol. 1998;11:477-84.


McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). Glycogen Storage Disease V. The Johns Hopkins University. Entry Number; 232600: Last Edit Date; 10/16/2002.

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Association for Glycogen Storage Disease

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