Pompe is classified as an autosomal recessive genetic disease that is acquired when a child inherits 2 altered GAA genes, 1 from each parent.
Mutations are variations or changes in a gene that result in changes to the sequence of that gene. The genes that make up our DNA are composed of 4 bases: A, T, G, and C. The 4 bases pair up in a specific way such that A can only pair with T and G can only pair with C. Even so, these 4 bases and 2 base pairing combinations can form many, many different arrangements that create our genes. Each gene has a specific sequence of these bases, like words have a specific order of letters. Like how words can be misspelled, genes can have “mistakes”: base substitutions, deletions, additions, that alter the normal sequence of the gene. The result of the various types of gene variants can range from those that change the sequence of the gene while partially preserving its function to those that cause complete loss of function. In Pompe disease, depending on the type of variant , GAA gene function can be deficient or completely absent.
GAA has the important function of breaking down glycogen (a complex sugar) into glucose (a simple sugar) inside cell lysosomes (small structures within the cells). When GAA is absent or lacking, glycogen accumulates in the muscles, resulting in symptoms of Pompe disease. Depending on both the extent of deficiency and residual enzyme activity, symptoms can appear as early as the first few months of life or years to decades later.
Pompe disease is rare, and current estimates put the incidence of occurrence at around 1 in 40,000 live births in the United States.
The incidence of a disease refers to the rate, or number, of new cases diagnosed in a given time period. The prevalence of a disease refers to the overall number of people affected with a particular disease. As with any rare disease, it is difficult to know exactly how many people are actually affected. It is estimated that the prevalence of Pompe disease may be 5,000 to 10,000 people worldwide. It occurs equally in males and females but varies depending on race and geographic location.
Many different genetic mutations or variations can affect the GAA gene. There are more than 500 gene variants although only about half are considered pathogenic, or disease-causing. Pathogenic variants that have been identified around the world are catalogued at the Pompe Centre at Erasmus MC. Individuals with Pompe disease may have the same gene variant (homozygous) or different gene variants (heterozygous), but most patients are likely to have more than 1 kind of GAA gene variant.
A carrier does not show any signs and symptoms of Pompe disease and is healthy. A carrier can, however, pass on the altered gene to their offspring. Let us look at a few possible scenarios.
When 2 healthy carriers of the GAA gene variant have a child, with each pregnancy their offspring have:
When a person with Pompe disease has a child with a person who is a carrier of Pompe disease, with each pregnancy their offspring have:
When a person with Pompe disease has a child with a person who is not a carrier of Pompe disease, with each pregnancy their offspring have: