What gene change causes Pompe disease?
Pompe disease is caused by a change (also called a mutation or a variant) in the GAA gene which causes the gene to not work correctly. The GAA gene carries the instructions for making the alpha-glucosidase enzyme, also called acid maltase, which is important for breaking down glycogen in the body. We normally have two working copies of GAA in our cells and we inherit one copy from our biological mother and the other from our biological father. In order to develop symptoms of Pompe disease, both copies of GAA are not working properly. This is also called autosomal recessive inheritance, which means that both parents of someone with Pompe disease are carriers of one working and one non-working copy of the GAA gene. Since each parent has one working copy, they don't have symptoms of Pompe disease themselves. However, when they have children, they each have a 1 in 2 or 50% chance of passing on the non-working copy to their child. When both parents are carriers, there is a 1 in 4 or 25% chance of both of them passing on the non-working copy and having a child with Pompe disease.
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What happens because of the GAA gene change?
When both copies of the GAA gene don't work correctly, the alpha-glucosidase or acid maltase enzyme cannot be made. Acid maltase is important for breaking down glycogen in certain compartments in muscle cells caused lysosomes, which are the "recycling center" of the cells. Without acid maltase, glycogen builds up in the lysosomes and causes damage to muscle cells. When enough muscle cells are damaged, the person with Pompe disease develops muscle weakness in the muscles needed for the body to move (skeletal muscles), the heart to pump (cardiac muscles), and the lungs to breathe (respiratory muscles).
Does anything make Pompe disease worse?
Pompe disease is a mendelian genetic disease, which means that it is primarily caused by one gene not working correctly (the GAA gene). It is possible that other genes, called modifiers, may affect the GAA gene's function and make symptoms better or worse in certain people; this is still being researched. Because Pompe disease affects the way muscles work, regular exercise, a heart-healthy diet, and avoiding smoking are encouraged. However, there are no known lifestyle factors that make Pompe disease better or worse.
- Acid Maltase Deficiency Association
What is creatine kinase and why is it elevated in Pompe disease?
Creatine kinase (CK) is an enzyme that is produced in all muscles. When muscles are being broken down because of a muscle disease, CK goes into the blood stream. Therefore, measuring CK in the blood can be an indication of whether a person has muscle breakdown. CK can be high for many reasons. If a person runs a marathon, they will likely have a high CK for a little while afterward because they had some mild muscle breakdown by running so long. However, if a person has a high CK without exercising and has some muscle weakness, it may be because of a muscle disease.
In Pompe disease, the CK is elevated due to muscle breakdown and can be over 10 times the normal range (less than 200 UI/L). People with late onset Pompe disease (LOPD) can have normal CK, but around 95% of the time it is elevated. It is important to remember that CK can be elevated for many reasons other than Pompe disease (it can be a measure of a heart attack because the heart muscle is breaking down, for example).
- Kishnani PS, Steiner RD, Bali D et al. Pompe disease diagnosis and management guideline. Genet Med 2006 8:267-88.
- Pompe Disease - Patients & Families: Getting Diagnosed https://www.pompe.com/en/patients/getting-diagnosed/tests.aspx