NORD gratefully acknowledges Tina K. Truong, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Glycogen storage diseases are a group of diseases where the body’s form of stored energy (glycogen) cannot be broken down into smaller pieces of sugars (glucose) for the body to use. People with glycogen storage disease type 7 (GSD7) usually have symptoms during childhood, but some people may have symptoms beginning as infants or later as adults. GSD7 symptoms are
GSD7 is caused by harmful changes (mutations) in the gene for muscle phosphofructokinase (PFKM) that leads to lowered activity (deficiency) in the phosphofructokinase enzyme, the protein that breaks down glycogen to glucose. The lack of this enzyme leads to a decreased amount of energy available to muscles during exercise. GSD7 is passed down in families in an autosomal recessive pattern of inheritance.
There is no specific cure or treatment for GSD7, but people with GSD7 are recommended to avoid heavy exercise and avoid eating meals with high amounts of carbohydrates.
GSD7 was first described by Tarui et al. in 1965 in three Japanese siblings. The siblings were easily tired and were not able to keep pace with other people. They had muscle weakness and stiffness in muscles used in heavy exercise.
There are four types of GSD7:
Childhood (Classic) GSD7
This is the most common form of GSD7 and usually begins in childhood with symptoms including:
Other symptoms can include:
Symptoms usually go away after rest.
This rare type of GSD7 occurs in babies. Symptoms include:
Late-onset (adult) GSD7
This form of GSD7 happens in adults who experience only muscle weakness and pain. They may have some muscle weakness and tiredness in childhood.
People with hemolytic GSD7 do not have muscle symptoms but have anemia due to break down of red blood cells.
GSD7 is caused by harmful changes (mutations) in the gene for muscle phosphofructokinase (PFKM). This leads to problems with the function of phosphofructokinase enzyme, the protein that breaks down glycogen to glucose. This lowered enzyme activity results in a decreased amount of energy for muscles to use during exercise. This leads to muscle pain and cramps.
GSD7 is inherited in an autosomal recessive manner. Recessive genetic conditions occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but will usually not show symptoms. The chance for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The chance to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
GSD7 is a rare disease that is seen more often in individuals of Japanese and Ashkenazi (Eastern European) Jewish ancestry. GSD7 affects males and females in equal numbers. The condition is estimated to occur is less than 1/1,000,000 people.
GSD7 is diagnosed by measuring the amount of the phosphofructokinase enzyme in a sample of muscle tissue taken from a muscle biopsy. It can also be diagnosed by measuring the phosphofructokinase enzyme level in red blood cells.
Lab tests after exercise can also show high levels of other proteins in the blood including creatinine kinase, lactate dehydrogenase, and aspartate transaminase.
Molecular genetic testing from a blood test can confirm changes in the PFKM gene.
The diagnosis of GDS7 is supported by high levels of ammonia and low levels of lactate in muscle biopsy or in blood removed from the forearm before and after exercise (forearm exercise test).
Heavy exercise should be avoided to prevent muscle pain and cramps. Eating simple sugars (carbohydrates) should also be avoided because this can make the exercise intolerance worse. Eating high amounts of protein during exercise may prevent symptoms.
Genetic counseling is recommended for individuals with GSD7 and their families.
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