What Is Pompe Disease?

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Pompe disease is a rare genetic condition that causes an abnormal buildup of glycogen, a sugar molecule, inside your cells. That buildup can impair how some of your organs and tissues function. The most commonly affected body areas are the heart, respiratory system, and skeletal muscles. Pompe disease can lead to weakness and breathing problems.

Every case of Pompe disease is different, but doctors can treat it successfully. Pompe disease goes by other names, including acid maltase deficiency (AMD), acid alpha-glucosidase (GAA) deficiency, and type II glycogen disease storage disease (GSD).

Here is what you need to need to know about Pompe disease, including types, symptoms, causes, diagnosis, and treatment.

Genetic Disorder
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Types of Pompe Disease

There are three types of Pompe disease, which will differ in their severity and the age of onset. These types are classic infantile-onset, non-classic infantile-onset, and late-onset.

Classic Infantile-Onset

Classic infantile-onset type appears within a few months of birth. Infants affected by Pompe disease will have muscle weakness, poor muscle tone, an enlarged liver, and/heart defects.

Classic infantile-onset Pompe disease makes it difficult for some infants to gain weight and grow at expected rates. Left untreated, Pompe disease can lead to death from heart failure in the first year of life.

Non-Classic Infantile-Onset

Non-classic infantile-onset type appears around 1 year of age. Little is known about this type of Pompe disease. But it is marked by delayed motor skills (such as delays in sitting up and holding the head up) and progressive muscle weakness.

While the heart muscle can be enlarged with this type of Pompe disease, it usually does not lead to heart failure. Muscle weakness, on the other hand, might cause severe breathing issues, and left untreated, non-classic infantile-onset Pompe disease can be fatal.

Late-Onset Pompe Disease

Late-onset type will appear later in a child’s life, in the teen years, or even in adulthood. It tends to be mild in comparison to the infant types. This form of Pompe disease is also less likely to involve the heart.

Many people with late-onset Pompe disease will experience progressive muscle weakness, usually in the lower limbs and the trunk (central part of the body). They may also experience problems with the muscles that control breathing.

As the disorder worsens, minor breathing difficulties may evolve into respiratory failure—a condition where the blood doesn’t have enough oxygen or too much carbon dioxide.

Pompe Disease Symptoms

What symptoms someone with Pompe disease will have, when they appear, and how life-altering they might be will vary from person-to-person. 

For example, babies who have classic or non-classic infantile-onset types will typically experience:

  • Weight gain problems and feeding troubles
  • Poor head and neck control
  • Late rolling over and sitting up
  • Breathing problems
  • Lung infections
  • Heart defects or an enlarged and thickening of the heart
  • An enlarged liver
  • An enlarged tongue

Older children and adults who develop late-onset Pompe disease will experience:

Late-onset Pompe disease tends to be progressive—meaning it will get worse with time.

Eventually, Pompe disease might affect the facial muscles, the muscles that support the spine, and muscles involved in eating and breathing. In adolescents, spinal muscle weakness can lead to scoliosis­—an abnormal curvature of the spine.

The severity of respiratory and breathing problems in late-onset Pompe disease varies and is often related to the diaphragm (the muscular and membranous structure separating the chest and abdominal cavities) and intercostal muscles (the muscles running between the ribs) weakness.

Late-onset Pompe disease usually doesn’t involve the heart.

Causes

In the United States, the prevalence of Pompe disease is around 1 in 40,000 people, according to the Cleveland Clinic. Men and women across all ethnic groups can be affected by this condition.

Pompe disease is an inherited condition where mutations in the GAA gene cause it to develop. It is inherited in an autosomal recessive pattern.

Autosomal recessive inheritance means you need both copies of the gene in each cell to have mutations. The parents of a person who has the inherited condition will each carry one copy of the mutated gene even though they do not have signs and symptoms of the disease.

The GAA gene is responsible for providing instruction to the acid alpha-glucosidase enzyme, which is active in the lysosomes—structures that support recycling within cells. Typically, the acid alpha-glucosidase enzyme breaks down glycogen into a simpler sugar called glucose that is the main energy source for the cells of the body.

When there are mutations in the GAA gene, acid alpha-glucosidase cannot break down glycogen and it will build up in dangerous amounts in the lysosomes. That buildup will eventually damage organs, muscles, and other tissues throughout the body.

There are no other known causes of Pompe disease.

Diagnosis

A diagnosis of Pompe disease can be made by assessing signs and symptoms of the condition, including poor muscle tone, frequent lung infections, and an enlarged heart.

Additional testing, including enzyme activity tests and genetic testing, can also help in making a diagnosis.

Enzyme Activity Tests

Enzyme activity tests can look for levels and activity of GAA enzymes. One way to check these levels is with a biopsy by taking a sample of muscle or skin tissue and examining it under a microscope to see much glycogen there is.

Blood tests can also determine GAA enzyme activity. This usually involves testing enzyme activity in white blood cells or by using a whole blood test.

Another blood testing method is a dried blood spot test, where a blood sample is taken and dried on a special filter and examined for abnormalities. The dried blood test is commonly used because it has found to be accurate and convenient.

People with Pompe disease will have higher than normal creatine kinase levels although CK level bloodwork isn't enough to confirm a diagnosis.

Genetic Testing

While enzyme activity tests are a main diagnostic approach, genetic testing may also be done to determine if someone has Pompe disease.

A DNA analysis—using blood or spit—can look for GAA gene mutations. A blood test can also help with mutation analysis— genetic testing targeted to detect a specific mutation.

Additionally, because Pompe disease is an inherited condition, your doctor or child’s doctor may want to identify other family members for GAA mutations.

Genetic counseling might help people make informed decisions about family planning, including those who might be at high risk of having a child with Pompe disease. 

Additional Testing

Your healthcare provider may order additional tests to assist in making a diagnosis and identifying problems associated with Pompe disease. This may include:

  • Pulmonary function tests to check breathing, respiratory function, and how well your lungs are working
  • Electromyograph to assess muscle injury and dysfunction
  • Electrocardiogram to detect abnormal heartbeat patterns and to make sure the heart muscle is working properly
  • Chest X-ray to determine if the heart is enlarged

Treatment

Early treatment, especially for infants, is vital for holding off the damage that Pompe disease can cause. While there is no cure for the condition, different treatments can ease symptoms of Pompe disease.

Enzyme Replacement Therapy

Enzyme replacement therapy (ERT) is the most commonly used treatment for Pompe disease. It can help to increase GAA enzyme levels in the body and reduce the accumulation of glycogen inside cells.

ERT uses a genetically engineered enzyme that acts similarly to the naturally occurring enzyme. It is given intravenously (through a vein).

ERT can reduce the abnormal thickening of the heart walls. It can also help with maintaining muscle function, which may translate to improvements in quality of life. Doctors try to give it early on before there is any significant muscle damage.

Research shows long-term ERT use can positively affect muscle strength, pulmonary function, and daily life activities, with a peak response period around two to three years after the start of treatment.

Sometimes, people with ERT will produce antibodies that reduce the effectiveness of the drug. However, there are medications available that can help to reduce this response.

Additional Therapies

Most people with Pompe disease will need supportive therapy to address respiratory and heart problems, physical disability, and swallowing problems associated with the condition.

Additional therapies include:

A Word From Verywell

Pompe disease is a genetic disease, so currently, it cannot be prevented. Fortunately, treatment is available for infants, children, and adults living with the condition.

The outlook for Pompe disease will depend on the type and the organs affected. Fortunately, new therapies can be effective in increasing the GAA enzyme and reducing glycogen levels. Research into ERT treatments and gene therapy continues to progress and is promising, which may improve the future outlook for many people with the condition.

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