Types of Pompe Disease

Pompe disease is a rare, inherited, and progressive disorder caused by mutations in the GAA gene. The disorder has three types: classic infantile-onset, non-classic infantile-onset, and late-onset Pompe disease. The three types differ based on the age at which symptoms first become apparent (called the age of onset), as well as their severity.

The GAA gene provides instructions for making an enzyme called acid alpha-glucosidase. This enzyme breaks down the complex sugar molecule glycogen into a simple sugar, glucose, which cells can metabolize for energy. In Pompe disease, due to the mutations in GAA, the enzyme either doesn’t function correctly or is fully absent, so glycogen builds up in tissues and causes damage — especially in muscles.

The type of Pompe disease is partially associated with the specific mutations in the GAA gene. In general, GAA mutations that lead to a total loss of function of the enzyme are associated with an earlier age of onset and more severe symptoms. By contrast, variants that produce an enzyme that works partially are linked with milder and later-onset disease.

Because all cases of Pompe disease are caused by GAA mutations, diagnosis and treatment strategies are similar among the three types. The main difference among them concerns the timing and severity of symptoms.

Classic infantile-onset Pompe disease

Symptoms of classic infantile-onset Pompe disease become apparent within the first few months of life, typically at around 4 months. People with this form of the disease typically have less than 1% of normal GAA enzyme activity.

Early symptoms often include poor feeding due to muscle weakness in the face and tongue, which leads to slow growth (failure to thrive). Other common early complications include delayed motor development, difficulty breathing, respiratory infections, and hearing loss.

Cardiomyopathy — disease of the heart muscle — is common in this type of Pompe disease, and usually may be apparent in the first weeks of life.

Without treatment, babies with classic infantile-onset Pompe disease usually do not survive past age 2, due to heart and/or respiratory failure. Enzyme replacement therapy (ERT) has been improving survival and other outcomes by reducing the accumulation of glycogen and curbing the progression of muscle damage.

Non-classic infantile-onset Pompe disease

Non-classic infantile-onset Pompe disease tends to begin within the first year of life, but later than the classic form that usually emerge within a few months of birth.

Common symptoms include progressive muscle weakness and delayed development of motor skills, such as rolling over and sitting up. Symptoms of non-classic infantile-onset Pompe disease generally are less severe than in the classic form. Some individuals will experience heart problems, such as an enlarged heart (cardiomegaly), but the progression of heart problems is usually slower than in the classic form.

Late-onset Pompe disease

When symptoms begin later in life, during childhood or adulthood, the disease is then known as late-onset Pompe. This form also is sometimes called juvenile/adult-onset Pompe disease. In people with this form of the disease, GAA enzyme activity typically is 40% or less of what is normal.

Muscle weakness, especially in the torso and legs, is well-known in this form of the disorder. Patients may develop a waddling or swaying gait, and may find it difficult to stand, run, or climbing stairs. Spinal muscular weakness may lead to scoliosis (a sideways curvature of the spine), especially in adolescents; it is not uncommon for patients to experience muscle cramps, as well as headaches and fatigue. Respiratory problems, due to weakness in the muscles used for breathing, also may develop.

In general, people whose symptoms appear later in life have less-severe manifestations that progress more slowly. Ultimately, prognosis for people with late-onset Pompe prognosis depends upon the extent of respiratory muscle involvement.


Last updated: June 3, 2021


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