Information on the following diseases can be found in the Related Disorders section of this report:

• glycogen storage disease type V
• Pompe disease
• Forbes disease

GSD type VII usually begins in childhood and is characterized by weakness, pain and stiffness during exercise, sometimes associated with nausea and vomiting and dark, burgundy-colored urine due to the presence of myoglobin (myoglobinuria). Destruction of muscle tissue (rhabdomyolysis) can also occur. A rare form of GSD type VII has been reported in infants that is associated with progressive loss of muscle tone (hypotonia), muscle weakness and death. A late-onset form has been reported in adults who experience only muscle weakness.

Glycogen storage disease type VII is caused by abnormalities (mutations) in the muscle phosphofructokinase gene that results in a deficiency of the phosphofructokinase enzyme. This enzyme normally converts fructose-6-phosphate to fructose-1,6-diphosphate. This is the controlling step in the breakdown of glucose into available energy and if the enzyme is deficient, energy is not available to muscles during heavy exercise. Consequently, pain and cramps occur in the muscle.

Glycogen storage disease type VII is inherited as an autosomal recessive genetic disorder. 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.

Glycogen storage disease type VII is a rare disorder that occurs more often in individuals of Japanese and Ashkenazi Jewish descent. GSD type VII affects males and females in equal numbers.

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 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. GSD 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).

Pompe disease is a hereditary metabolic disorder caused by the complete or partial deficiency of the enzyme acid alpha-glucosidase (also known as lysosomal alpha-glucosidase or acid maltase). This enzyme deficiency causes excess amounts of glycogen to accumulate in the lysosomes of many cell types but predominantly in muscle cells. The resulting cellular damage manifests as muscle weakness and/or respiratory difficulty. Pompe disease is also classified as glycogen storage disease type II (GSD II).

Forbes disease (GSD-III) is one of several glycogen storage disorders that are inherited as autosomal recessive traits. Symptoms are caused by a lack of the enzyme amylo-1,6 glucosidase (debrancher enzyme). This enzyme deficiency causes excess amounts of an abnormal glycogen (the stored form of energy that comes from carbohydrates) to be deposited in the liver, muscles and, in some cases, the heart.

For more information on the above disorders, choose "Glycogen Storage Disease Type V," "Pompe" and "Forbes" as your search terms in the Rare Disease Database.

Diagnosis
GSD type VII is diagnosed by a muscle biopsy for measurement of the phosphofructokinase enzyme level or measurement of the phosphofructokinase enzyme level in red blood cells. Molecular genetic testing for the phosphofructokinase gene mutations prevalent in the Ashkenazi Jewish population are available on a research basis.

Treatment
Strenuous exercise should be avoided to prevent muscle pain and cramps. Consumption of carbohydrates should be avoided because this can exacerbate exercise intolerance.

Genetic counseling is recommended for affected individuals and their families.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. 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 National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Weinstein DA, Koeberl DD and Wolfsdorf JI . Type VII Glycogen Storage Disease. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:456-7.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 232800; Last Update: 5/31/05.

Chen Y-T. Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, et al., eds. The metabolic and molecular basis of inherited diseases. New York: McGraw-Hill, 2001:1521-1551.

DiMauro S, Bruno C. Glycogen storage diseases of muscle. Curr Opin Neurol 1998:11:477-484.