What is Pompe Disease?

Pompe disease is a rare genetic disorder characterized by the abnormal buildup of a complex sugar molecule called glycogen inside cells. This buildup impairs the workings of different organs and tissues, especially the heart and other kinds of muscle.


Glycogen is a form of sugar that the body stores mainly in the cells of the liver and skeletal muscles, where it works as a long-term reserve of energy. When the body needs energy, this large molecule is broken down into glucose, in a process that requires certain proteins — known as enzymes. One of these enzymes is the acid alpha-glucosidase (GAA).

The instructions for making the GAA enzyme are encoded in a gene, also called GAA. A mutation in the GAA gene can either lead to the production of a GAA enzyme that doesn’t work correctly, or prevent the production of the enzyme entirely. In people with Pompe disease, glycogen cannot be broken down and builds to toxic levels inside cells. Muscle cells are especially affected because glycogen normally serves as a main source of energy to power muscle movements.


Every person inherits two copies of the GAA gene, one from each biological parent. Pompe disease is inherited in an autosomal recessive pattern. This means the disease only develops in people who have mutations in both copies of the GAA gene.

People who have one mutated GAA gene, and one normal gene, do not show any signs or symptoms of Pompe disease. However, these individuals can pass the disease-causing mutation to their biological children; for this reason, they are called “carriers” of the disease.

If two carriers have biological children, there is a one in four or 25% chance that a child will inherit both mutated copies of the gene and develop Pompe disease. Likewise, there is a 50% chance that the child would inherit one mutated gene and one normal gene — so the child would be a carrier like their parents — and a 25% chance that the child will inherit two normal GAA genes, and so would not have the disease or be a carrier.


There are three types of Pompe disease, classified according to the disorder’s severity and age of onset. They are the classic infantile form, non-classic infantile form, and late-onset form.

Symptoms of classic infantile Pompe disease are evident within months of birth, while symptoms of the non-classic infantile form usually start to develop by a child’s first year of life. Late-onset Pompe may begin anytime from late childhood to adolescence, or even in adulthood.

Broadly, the type of Pompe disease a person develops partially depends on the type of GAA mutations they have: people with mutations that lead to a complete lack of GAA enzyme activity usually have more severe disease (i.e., classic infantile form), while those with some reduced GAA activity have more mild disease (i.e., late-onset form).


Symptoms of the classic infantile-onset form of the disease include a slower growth rate (often due to feeding problems), muscular weakness, poor muscle tone, and poor or absent reflexes. Difficulties breathing, moving, and swallowing also are common symptoms, as are an enlarged tongue, liver, and heart. Without treatment, these patients often die at very young ages — 1 or 2 years old — due to heart or breathing complications.

In non-classical infantile Pompe disease, damage to the heart muscle tends to progress more slowly than in children with the classic form. Muscle weakness and delays in motor development are also common in babies with this form of Pompe.

As for the late onset form of Pompe, symptoms include slow but progressive muscular weakness — particularly of muscles in the legs, trunk, and respiratory system — motor difficulties, breathing problems, and fatigue. Some patients will develop scoliosis, which is a sideways curvature of the spine. Life expectancy can be affected, but the disease’s prognosis varies substantially person-to-person.


Pompe disease is typically first suggested by clinical findings, particularly those related to breathing problems and evidence of muscular weakness. A differential diagnosis (distinguishing between different diseases with similar symptoms) is important, since Pompe disease may be wrongly assumed to be another disorder that causes muscle wasting.

A diagnosis can be confirmed by assessing the activity of the GAA enzyme in cells obtained from the skin, muscles, or blood. In children with infantile-onset Pompe disease, the activity of the GAA enzyme is generally less than 1% of normal. In individuals with the late-onset form of this disease, GAA activity is typically lower than 40% of normal.

Testing for GAA gene mutations can help confirm the diagnosis, and is particularly helpful in identifying carriers. For people who are known carriers of the disease, genetic testing before the baby is born (prenatal testing) may be available.

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