The Spectrum of Pompe Disease

Pompe disease is a genetic disorder that is always present at birth. However, symptoms may show up at any time from infancy through adulthood. Here are two example cases:

A three-month-old baby, who seemed normal at birth, is diagnosed with an enlarged heart. At six months he cannot sit up without support. He became very weak and needed a feeding tube to help him gain weight. He was diagnosed with “infantile-onset” Pompe disease.
A 37-year-old man suddenly starts falling asleep during the day and has trouble breathing when he is lying down. After two years of being tested and examined, he is diagnosed with “late-onset” Pompe disease. Looking back, he can recall that even though he was active in sports as a child, he could never quite keep up with the other kids on the team. Now he uses a ventilator at night to help him breath. He is still driving and working full-time.

One of the striking features of the disease is how much it varies from one person to another in terms of:

The age at which symptoms first appear
The rate at which the disease progresses
The degree to which other organs are affected

What are the different forms of Pompe disease?

While the disease is the same, medical professionals often classify the way the disease progresses into “forms of the disease.” Pompe disease is broadly divided into two groups:

Infantile-onset Pompe disease

Children with infantile-onset Pompe disease usually show symptoms of the disease during the first few months of life. This classic form of infantile-onset Pompe disease progresses rapidly and is almost always fatal before 1 year of age.

Some children have an atypical form of infantile-onset Pompe disease in which symptoms show up later in the first year of life. In these children, damage to the heart muscle progresses more slowly, and they may survive past their first birthday. more>

About one-third of all people born with Pompe disease have the infantile-onset form.

Late-onset Pompe disease

Children and adults whose symptoms show up after 1 year of age may receive a diagnosis of late-onset Pompe disease. The late-onset form of the disease tends to progress more slowly than the infantile-onset form but can present significant challenges as muscle weakness increases. more>

There is no data currently available to suggest mental development is affected in either form of the disease.

Approximately two-thirds of all people born with Pompe disease have the late-onset form.

Level of Enzyme Activity

This graph illustrates the level of acid alpha-glucosidase enzyme activity in the two forms of Pompe disease. Pompe disease is typically more severe in people who have lower levels of enzyme activity.

The GAA enzyme breaks down glycogen in the lysosomes of muscle cells. Researchers have found that:

Infantile-onset patients generally have less than 1% of normal GAA enzyme activity
Late-onset patients generally have less than 40% of normal GAA enzyme activity when measured in cultured skin fibroblast cells

Pompe disease is typically more severe in people who have lower levels of residual GAA activity. The disease progresses rapidly in infantile-onset patients who have little or no enzyme activity.

By contrast, Pompe disease tends to progress more slowly in children and adults with late-onset disease who have at least a small amount of residual GAA activity. The level of enzyme activity may relate to the presence of heart problems, which is a key feature of the infantile-onset form of the disease. Most patients who develop symptoms later in life typically have a higher level of residual enzyme activity. Different from infantile onset cases, the vast majority of patients with later onset do not have clinical evidence of cardiac involvement.