Pompe Disease

Updated August 20, 2019

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Pompe (pom-PAY) disease is a glycogen storage disorder caused by an enzyme that does not work to break down glycogen.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic.

Because this enzyme is either missing or not working properly, glycogen will build up and create symptoms related to muscles getting progressively weaker.

Since symptoms will vary from one person to another, treatment will vary, too.

Although this disease is often classified as glycogen storage disorder, it also belongs to the group of disorders called lysosomal storage disorders, another type of genetic disorder caused by enzymes that do not function properly.

At Your DNA, we’ve reviewed the latest scientific literature on rare genetic diseases to help you get a deeper understanding of Pompe disease.

What Is Pompe Disease?

Pompe disease, also known as glycogen-storage disease type II and acid maltase deficiency 1, is a rare genetic disorder caused by glycogen, a complex sugar, building up in cells.

Essentially, a mutation in the GAA gene creates a deficiency of acid alpha-glucosidase (GAA), the enzyme that breaks down glucose in the cells.

As glycogen builds up in tissues, it causes muscles to break down. As muscles get progressively weaker, many vital functions in the body, like breathing and heartbeat, become difficult.

Since Pompe disease creates an excessive amount of glycogen in cells, doctors treat patients with enzyme replacement therapy 2, giving them intravenous drips of recombinant human acid alpha-glucosidase.

This does the work that the natural enzyme can't.

Types of Pompe Disease

Researchers have identified three variations of Pompe disease, differentiating them by age of onset and severity.

Researchers call the first type classic infantile-onset; the second, non-classic infantile-onset; and the third, late-onset.

How Common Is Pompe Disease?

Pompe disease is rare. It only affects one person out of 40,000 in the United States, affecting all ethnic groups and both males and females equally.

Signs & Symptoms of Each Type of Pompe Disease

Classic infantile-onset Pompe disease begins a few months after birth 3. If doctors do not treat the disease, a child will die within the first year of life.

Common symptoms include:

  1. Myopathy or muscle weakness
  2.  Hypotonia or poor muscle tone 
  3.  Hepatomegaly or an enlarged liver 
  4.  Heart defects 
  5.  Failure to gain weight 
  6.  Failure to thrive, i.e. the child does not grow at the expected rate
  7. Trouble breathing

Non-classic infantile-onset Pompe disease begins at age one. Even with treatment, a child will likely only live into early childhood because their muscles get increasingly weaker.

Common symptoms include:

  1. Delayed motor skills to roll or sit
  2.  Muscles get progressively weaker
  3.  Cardiomegaly, or an abnormally large heart (but this does not lead to heart failure)
  4. Increased breathing problems

Late-onset Pompe disease can begin in late childhood, in adolescence, or even in early adulthood.

This form is milder than the other two types and does not typically weaken the heart.

The primary symptom is progressive muscle weakness in the legs, upper body, and the muscles involved in breathing. Over time, muscle weakness may cause respiratory failure.

Causes of Pompe Disease

How do you get Pompe disease? Since it's a genetic condition, you can only inherit it from a parent. However, it is common for neither parent to exhibit any symptoms because they may only have one copy of an abnormal gene.

The disease is caused by a mutation — a change in a gene. The mutated gene does not make acid alpha-glucosidase, an enzyme necessary for the breakdown of glucose in cells.

Because the enzyme does not break glycogen down, it accumulates and stops the cells from working properly.

This excess glycogen then builds up in the body and weakens muscles, including muscles of the heart and the muscles necessary for breathing.

Inheritance Pattern of Pompe Disease

People inherit Pompe disease through an autosomal recessive pattern. Each cell in a patient’s body has both copies of the mutated gene.

If parents are healthy carriers, they don't show any signs of the disease, because each parent may only carry one mutated copy of the gene.

Can I Be a Carrier?

Is it possible that you or your partner are a Pompe disease carrier? Other than testing, the only way you would know is if you already have a child with Pompe disease.

Statistically, however, it’s highly unlikely. Pompe disease carrier frequency is extremely low. In the U.S., only one in 40,000 people have the disease.

If for some reason you are concerned that you could be a healthy carrier and could have a child who would inherit the disease, then consider getting genetic counseling.

You will get information about inheritance and the genetic risks of having a child, as well as guidance on how to get the right genetic test.

Risk Factors for Pompe Disease

The only risk factor for Pompe disease is if you have a genetic predisposition to develop it. A genetic predisposition occurs when you inherit specific genetic patterns from your parents.

However, even if you have a predisposing genetic variation because your parents were both healthy carriers, this still does not mean that you'll get the disease.

Often people with a predisposing genetic variation for a disease only carry one copy of the mutated gene in their cells and so never get the disease.

Who Does Pompe Typically Affect?

In the United States, only one in 40,000 births will get Pompe disease. Unlike other genetic diseases, it does not appear more concentrated in some ethnic groups than others or more in one gender more than the other.

Pompe disease appears to affect all populations around the world and all ethnic groups. It also appears in both sexes in equal numbers.

Diagnosis of Pompe Disease

A doctor will do a comprehensive physical examination and review patient and family history when doing a Pompe disease diagnosis 4.

After the diagnosis, the doctor will also take a blood sample to rule out Pompe disease false positives.

A medical technician will confirm if there is a GAA deficiency by doing acid alpha-glucosidase (GAA) enzyme activity assays 5.

Newborn Screening by State

Most states rely on Health Resource Service Administration (HRSA) guidelines to decide what to focus on when screening newborns. However, some states test for disorders that are not part of HRSA.

Most states test newborns for common conditions like hearing loss, heart disease, sickle cell disease, cystic fibrosis, phenylketonuria (PKU), and so on

Some states also test for rare genetic conditions, including Pompe disease.

If your state does not test for Pompe disease, you can ask your health care provider for expanded supplemental screening for newborns, which will be done by a commercial laboratory.

Although this test will be different than the one done by your state, the laboratory may use the same blood sample — so it may only be necessary to draw blood once for a sample to be used for both state and newborn supplemental screening.

Can Pompe Disease Be Diagnosed Before a Baby Is Born?

It is possible to get a diagnosis of a genetic disorder like Pompe disease before a baby is born.

Usually, parents who want to see if their child is at risk have a good reason for making this request.

Either they have discovered that they are a healthy carrier and carry one copy of the genetic mutation or another child in their family already has Pompe disease.

Testing for Pompe Disease

If there is a good reason to believe that you are either a healthy carrier or may have Pompe disease, then a doctor will recommend testing. Many types of tests are possible, but the most common types are blood tests.

One type of blood test is to evaluate how much acid alpha-glucosidase enzyme is available in your blood.

If it is lower than normal or your blood does not show any of this enzyme activity at all, then it indicates you may have Pompe disease.

Is Genetic Testing Available?

Genetic testing is available for confirming Pompe disease.

What Other Testing Is Available?

Hospitals screen newborns for many diseases, and in some states, they screen newborns for Pompe disease.

If a state does not provide newborn screening for this disease, parents can ask for newborn supplemental screening.

Besides blood tests, there are many other tests available:

  • Sleep study tests measure problems associated with sleeping
  • Breathing tests measure lung capacity
  • Electromyography tests measure how well muscles work
  • DNA testing checks the gene that produces the enzyme necessary for glucose assimilation
  • Electrocardiograms, X-rays, and Echocardiograms measure the efficiency of the heart to pump blood

Where to Get Tested

Many highly specialized hospitals and clinics throughout the United States diagnose and evaluate genetic conditions like Pompe disease.

Three examples of places where you can get tested for Pompe disease are UC Health in metro Denver, the Mayo Clinic, and Duke Health.

UC Health in metro Denver offers genetic testing that can diagnose and evaluate your genetic condition and then work with you and your family care physician to manage any conditions you have.

Mayo Clinic's Department of Clinical Genomics has a slightly different approach. Medical geneticists, certified genetic counselors, and other medical professionals will work as a team. They will evaluate your genetic condition by coordinating a wide range of medical procedures and laboratory tests.

Duke Health scientists are pioneering some Pompe disease research and have developed a special gene therapy that may replace the current FDA approved treatments.

Treatment Options for Pompe Disease

The FDA has approved enzyme replacement therapy for Pompe patients.

Patients receive an alpha-glucosidase drug administered intravenously that is genetically engineered to act just like the natural acid alpha-glucosidase enzyme.

Pompe Disease Treatment Cost

The cost for treatment is over $500,000. Besides the cost of the hospital, there is the cost of the medical team and the medication.

After doctors diagnose an older child with Pompe disease, an entire support team is necessary to provide comprehensive treatment.

A child’s team of medical specialists might include a cardiologist, a neurologist, a dietitian, a respiratory therapist, a physical therapist, and an occupational therapist.

The FDA approved Lumizyme as a medication in 2010 for late-onset Pompe disease. According to the manufacturers, Sanofi Genzyme, this costs about $298,000 a year.

Complications of Pompe Disease

Unless infants get treatment for Pompe disease, they will usually die within the first year.

Those with the disease who do get treatment still have numerous complications because their progressive muscle weakness causes heart and respiratory problems.

The progressive muscle weakness is so debilitating that most people with the disease will eventually need oxygen tanks and a wheelchair.

Prognosis for Pompe Disease

Is Pompe disease fatal? The outlook for Pompe disease depends upon when it shows up and how quickly and comprehensively it is treated.

If it shows up in infancy and a child does not receive quick treatment, then it is fatal because it progresses rapidly.

However, research shows that early treatment because of newborn screening detection can be beneficial 6.

Generally speaking, the later the onset of Pompe disease, the slower it will progress.

The average life expectancy for someone with late-onset Pompe disease is about 30 years.

If, however, the disease appears when they're teenagers, then the Pompe disease life expectancy in an adult is likely to be 50 years.

What to Do Next

It's hard for any family to recognize and come to terms with the fact that their child has Pompe disease.

However, if your child does have Pompe disease, you don't have to go it alone. There are teams of medical professionals who can help your child and your whole family cope with the disease.

Here are some organizations that can provide information or support:

  • Acid Maltase Deficiency Association 
  •  National Organization for Rare Disorders
  •  International Pompe Association 
  •  Pompe Community
  •  United Pompe Disease Foundation

At present, prevention of Pompe disease is not possible, and only treatment and care options are available.

However, in the future, breakthroughs in genomics might make it possible for the body to bypass the malfunction of the GAA gene.

For instance, researchers at Duke University have successfully created an experimental therapy that uses a mutated virus to deliver a gene to the liver.

Once at the liver, the gene will produce the GAA enzyme that is missing in people who have Pompe disease.

Having Pompe Disease

If you have Pompe disease, then the best treatment to date is to use enzyme replacement therapy.

This is an FDA-approved treatment plan for all patients with Pompe disease. However, this alone is not enough.

You will also need supportive therapies.

  • A physical therapist will help you strengthen your respiratory muscles to avoid respiratory failure.
  • An occupational therapist will help you learn how to use a cane, walker, or wheelchair.
  • A speech therapist can help to improve articulation and speech.
  • An orthopedist may help you use orthopedic devices like braces.
  • A surgeon may help you if you have orthopedic symptoms like contractures or spinal deformity.
  • A nutritionist may help you with proper nutrition and maintaining proper body weight.

Carriers for Pompe Disease

Healthy carriers of the condition don’t show any symptoms because their cells have one normal gene and one abnormal gene.


Pompe disease is inherited because it is an autosomal recessive genetic trait. It's a single disease continuum with variable rates of severity, and there are different ages of onset, starting with infantile-onset Pompe disease.

As muscles get progressively weaker, it not only causes mobility issues and issues with chewing and swallowing foods but it also affects respiratory and heart functions.

Pathogenic variations in the GAA gene, change the information necessary for the production of acid α-glucosidase (GAA).

Research in enzyme replacement therapy appears promising and current symptomatic treatment includes receiving recombinant human acid alpha-glucosidase drugs intravenously.

Supportive treatment includes the coordinated efforts of health care professionals like dietitians, cardiologists, orthopedists’ neurologists, internists, pediatricians, and others.

Genetic counseling is also helpful, not only for those affected by the disease but also for the whole family.

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Referenced Sources

  1. Pompe's disease.
    van der Ploeg AT, Reuser AJ. October 11, 2008.
  2. The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature.
    van den Hout HM, Hop W, van Diggelen OP, Smeitink JA, Smit GP, Poll-The BT, Bakker HD, Loonen MC, de Klerk JB, Reuser AJ, van der Ploeg AT. August, 2003.
  3. Infantile-Onset Pompe Disease Natural History Study Group. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease.
    Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D, J Pediatr. May, 2006.
  4. Pompe disease diagnosis and management guidelines.
    Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE, Crowley JF, Downs S, Howell RR, Kravitz RM, Mackey J, Marsden D, MartinsAM, Millington DS, Nicolino M, O'Grady G, Patterson MC, Rapoport DM, Slonim A, Spencer CT, Tifft CJ, Watson MS. May 2006 and June 2006.
  5. Diagnosis of glycogenosis type II.
    Bembi B, Cerini E, Danesino C, Donati MA, Gasperini S, Morandi L, Musumeci O, Parenti G, Ravaglia S, Seidita F, Toscano A, Vianello A. December 2, 2008.
  6. Pompe disease in infants: improving the prognosis by newborn screening and early treatment.
    Chien YH, Lee NC, Thurberg BL, Chiang SC, Zhang XK, Keutzer J, Huang AC, Wu MH, Huang PH, Tsai FJ, Chen YT, Hwu WL. December, 2009.