Glycogen storage diseases are a group of disorders in which stored glycogen cannot be metabolized into glucose to supply energy for the body. Glycogen storage disease type VII (GSD VII) is characterized by weakness, pain and stiffness during exercise. GSD VII is caused by abnormalities in the muscle phosphofructokinase gene that results in a deficiency of the phosphofructokinase enzyme. This enzyme deficiency leads to a reduced amount of energy available to muscles during exercise. GSD VII is inherited as an autosomal recessive genetic disorder.
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.
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.
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.
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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.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 232800; Last Update: 5/31/05.