Inheriting Pompe Disease

Pompe disease is a genetic disease, meaning it is caused by a defect in a person’s genes. Genes control many aspects of the body, including production of important enzymes. Pompe disease is inherited when both parents pass on a gene called GAA that has a mutation, or defect, resulting in deficiency or the malfunction of GAA enzyme.

The Cause of the Disease

The underlying cause of Pompe disease is an absence or marked defiency of a specific enzyme, acid alpha-glucosidase (also known as GAA). This absence or marked defiency leads to excessive buildup of a substance called glycogen within muscle cells.

The GAA gene is responsible for the production of the GAA enzyme, which is needed to break down a substance called glycogen that can accumulate inside cell lysosomes (small structures within the cells). If there is a defect in this gene, the enzyme may be deficient or not function properly. As a result, excessive amounts of glycogen build up in the lysosomes, causing symptoms of Pompe disease.

Learn more about the underlying cause of Pompe disease 

Take Note: The GAA Gene

The gene responsible for Pompe disease was identified in 1979 and named glucosidase acid alpha. The abbreviation GAA is often used interchangeably to refer to both the gene and the enzyme involved in Pompe disease.

Defining Who Has the Disease

Every gene in the body comes as a pair: one copy is passed on by the father and one by the mother. The combination of GAA genes inherited from both parents determines whether a person will be affected by Pompe disease:

  • If both genes in the pair are normal (no defect), the person will not have the disease.
  • If both genes in the pair have the defect, the person will have the disease.
  • If one gene is normal and one has the defect, the person will be a carrier. Carriers do not have Pompe disease, but they “carry” the gene defect and may pass it on to their own children.

 Figure 1. Autosomal Recessive Inheritance

 

Pompe disease is inherited in an autosomal recessive manner. Thus, both parents of a child with the disease must be carriers of a mutant gene for GAA, and each child born to them has a 25% chance of having the disease, a 50% chance of being a carrier, and a 25% chance of neither having the disease nor being a carrier.

Status of Carriers

Although Pompe disease carriers have one defective GAA gene, their other normal copy of GAA gene allows for the production of enough enzyme to keep cells functioning properly. Their enzyme activity is usually somewhat lower than normal, but they do not experience any symptoms.

The Odds of Inheriting Pompe Disease

The most common inheritence scenario which results in Pompe disease is when both parents are carriers. In this case, with each pregnancy the chances are:

  • 1 in 4 (25%) that the child will receive two defective genes and thus inherit the disease
  • 2 in 4 (50%) that the child will inherit only one defective gene and become a carrier
  • 1 in 4 (25%) that the child will be completely unaffected

Far less common inheritance scenarios include:

  • If both parents have Pompe disease, then every child will inherit the disease
  • If one parent has the disease and the other is a carrier, each child has a 50% chance of inheriting the disease and a 100% chance of being a carrier

See statistics on how many people have Pompe disease 

Note that if one parent has Pompe disease and the other parent does not (and is also not a carrier), all children will be carriers (because they will always inherit one defective and one normal gene), but none of them will have the disease.

Take Note: Autosomal Recessive

Pompe disease is an autosomal recessive genetic disorder because:

  • The GAA gene is found on an autosome—a chromosome not related to determining gender.
  • The GAA gene is recessive, meaning that one defective gene alone will not cause the disease—both genes in the pair must be affected.

For more details on genes and chromosomes, visit the Understanding Genetics page

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