Pompe disease overview
Fact-checked by
A rare genetic disorder, Pompe disease is characterized by the abnormal buildup, inside cells, of a complex sugar molecule called glycogen. This buildup impairs the workings of different organs and tissues, especially the heart and other kinds of muscle.
Pompe disease also is known as glycogen storage disease type 2 (GSD2).
What are the symptoms of Pompe disease?
Pompe disease symptoms among patients can vary greatly, based on the person’s age at disease onset, the type of Pompe disease, and the rate of disease progression and severity.
The most common symptoms associated with Pompe disease are:
- Progressive muscle weakness
- Poor muscle tone
- Breathing problems
- Respiratory infections
- Trouble eating
- Enlargement of the tongue, liver (hepatomegaly), and/or heart (cardiomegaly)
- Hearing impairment.
What are the types of Pompe disease?
Pompe disease is classified into three types:
- Classic infantile-onset form
- Nonclassic infantile-onset form
- Late-onset form.
Classic infantile-onset Pompe disease
Babies with classic infantile-onset Pompe disease start to exhibit symptoms such as difficulty feeding, poor muscle tone, and delayed motor development within the first few months after birth. Heart disease (cardiomyopathy) usually develops within the first weeks of life. Difficulty breathing and hearing loss also are common.
Nonclassic infantile-onset Pompe disease
In this form of Pompe disease, symptoms become apparent within the first year of life, with babies showing muscle weakness and delayed motor development. Symptoms of nonclassic infantile-onset Pompe disease usually develop later than in the classic form, and unlike the classic form, babies with nonclassic infantile-onset Pompe do not develop cardiomyopathy within the first year of life. For this reason, some classification systems consider this form of Pompe disease to be a subtype of the late-onset form.
Late-onset Pompe disease
Late-onset disease is used to refer to Pompe disease when symptoms develop at any point after the first year of life. Some people with late-onset Pompe develop symptoms in childhood, while others don’t experience symptoms until the latter decades of life — the reason why this type is sometimes called adult-onset Pompe disease.
Generally, a younger age at onset is associated with more severe disease. People with late-onset Pompe disease typically experience progressive muscle weakness, especially affecting the torso and legs. Breathing problems also may develop as the disease progresses.
What causes Pompe disease?
Glycogen is a form of sugar the body stores mainly in 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 the acid alpha-glucosidase (GAA) enzyme.
Pompe disease is caused by mutations in the GAA gene that encodes instructions for making the GAA enzyme. 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.
How is Pompe disease treated?
Pompe disease patients are usually cared for by a multidisciplinary team of specialists to ensure all aspects of the disorder are treated. This team typically includes cardiologists, neurologists, pulmonologists, respiratory therapists, dietitians, orthopedists, occupational/speech therapists, geneticists, and genetic counselors.
Pompe disease treatment is based on:
- Disease-specific treatments, including enzyme replacement therapy and Pombiliti + Opfolda
- Supportive therapies.
Several experimental treatments for Pompe disease are now in development, including therapeutic approaches based on gene therapy. The aim of gene therapy in Pompe disease would be to provide the body a working copy of the GAA gene.
Enzyme replacement therapy
Known as ERT, enzyme replacement therapy involves providing Pompe patients with an engineered version of the GAA enzyme to replace the missing or nonworking enzyme. The treatment is designed to help reduce the toxic buildup of glycogen inside cells, thereby slowing the progression of the disease.
There are two ERT medications for Pompe disease that are widely available; both are sold by Sanofi. These are:
- Lumizyme (alglucosidase alfa), sold under the brand name Myozyme outside the U.S., which is approved in the U.S., Canada, the European Union, and other markets for all types of Pompe disease.
- Nexviazyme (avalglucosidase alfa), a next-generation therapy that is approved for patients ages 1 year and older in the U.S.; it also is approved in other markets, including the EU and Canada, though age ranges vary.
Enzyme replacement therapy with enzyme stabilizer
The combination therapy Pombiliti (cipaglucosidase alfa) + Opfolda (miglustat) has also been approved in the U.S., EU, and U.K. for certain adults with late-onset Pompe disease. It is marketed by Amicus Therapeutics. Its components are cipaglucosidase alfa (Pombiliti), a form of the GAA enzyme, and miglustat (Opfolda), an enzyme stabilizer. This two-step approach works primarily to improve walking ability and at least stabilize respiratory function.
Supportive therapies
Healthcare providers also can prescribe treatments to help manage specific Pompe symptoms.
Nondrug treatments, such as physical therapy, occupational therapy, and speech therapy, may be of benefit for some people with Pompe disease. Physical therapy, in particular, may help to strengthen muscles (especially respiratory muscles) and a person’s overall physical condition.
How is Pompe disease inherited?
People inherit two copies of the GAA gene, one from each biological parent. Pompe disease is inherited in an autosomal recessive fashion, meaning the disease will only develop in offspring if both copies of the GAA gene are mutated. A person with only one mutated copy is referred to as a Pompe disease carrier. These patients will not develop the disease, but may pass the Pompe-causing mutation to their biological children.
If two carriers have biological children, there is a one in four (or 25%) chance that each child would inherit both mutated copies of the gene and develop Pompe disease. Likewise, there is a 50% chance that any children would inherit one mutated gene and one normal gene — so the children would be carriers like their parents. There also is a 25% chance that a child would inherit two normal GAA genes, and so would not have the disease nor be a carrier.
How is Pompe disease diagnosed?
Pompe disease can be suggested by clinical findings, particularly those related to breathing problems and evidence of muscular weakness. A differential diagnosis — one that distinguishes between different diseases with similar symptoms — is important, because Pompe disease may be wrongly assumed to be another disorder that causes muscle wasting, and thus misdiagnosed.
Confirming a diagnosis of Pompe disease usually involves enzymatic tests to measure the activity of the GAA enzyme. 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.
Genetic testing to look for disease-causing mutations in the GAA gene 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 and help ensure an early diagnosis.
What is the prognosis of Pompe disease?
Prognosis and life expectancy in Pompe varies substantially from person to person, depending on disease type and specific clinical characteristics. Generally, mutations that lead to greater functional impairment of the GAA enzyme are associated with more severe disease. Specifically, worse impairments are tied to an earlier age at onset and faster symptom progression.
Without treatment, babies with classic infantile-onset Pompe disease typically don’t survive past age 2, and most children with the nonclassic infantile-onset form survive only into early childhood. In the classic type, symptoms usually begin within a few months of birth. For those with late-onset Pompe, the prognosis is largely dependent on the extent to which the disease causes breathing problems.
Notably, novel treatments such as ERT or Pombiliti + Opfolda are improving outcomes for people with all forms of Pompe disease. Specific Pompe treatments have only been available for a decade or two, however, so the long-term prognostic outlook for treated patients is still not completely understood.
What other conditions could Pompe disease be mistaken for?
A number of other health conditions may cause muscle weakness and other symptoms commonly associated with Pompe. These include other glycogen storage disorders, which, like Pompe disease, are characterized by a toxic buildup of glycogen. Other disorders affecting muscle health also may be associated with Pompe disease.
In babies with infantile-onset forms of Pompe disease, symptoms may resemble:
- Glycogen storage disease type 3a, also called debrancher deficiency
- Glycogen storage disease type 4, also known as branching enzyme deficiency
- Heart diseases such as myocarditis, characterized by inflammation in the heart’s tissue
- Spinal muscular atrophy (SMA) type 1
- Danon disease
- Carnitine uptake disorder
- Disorders that impair the activity of mitochondria, the powerhouse of the cell.
Late-onset forms of Pompe disease may resemble:
- Glycogen storage disease type 5, known as McArdle disease
- Glycogen storage disease type 6, also called Hers disease
- Muscular dystrophies, a group of genetic disorders that cause progressive muscle weakness
- Polymyositis.
Pompe Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Pompe disease
Despite the approvals of specific therapies for Pompe disease, no cure is available. Still, Pompe patients can benefit from enzyme replacement therapies, designed to slow the progression of the disease by reducing the toxic buildup of glycogen inside cells, as well as from the combination therapy Pombiliti + Opfolda. Supportive treatments like physical therapy and occupational therapy also can be of help in navigating life with Pompe disease.
The estimated incidence (the number of new cases in a given time period) of Pompe disease varies in different locations and among ethnic groups. In the U.S., Pompe disease affects about 1 of every 40,000 people overall, though the rate is higher — 1 of every 14,000 — among African Americans. Among people of European descent, late-onset Pompe affects 1 in every 60,000 people, while infantile-onset Pompe affects about 1 in 100,000 individuals. In southern China and Taiwan, the incidence of Pompe disease has been estimated at 1 in every 50,000 people, while in Australia, the estimated incidence is 1 in 145,000.
In the U.S., the federal government recommends checking newborns for a number of serious genetic disorders that can be tested for shortly after birth; these diseases are listed on the recommended uniform screening panel (RUSP), to which Pompe was added in 2015. While the U.S. government recommends screening for all disorders on the RUSP, each state ultimately decides what conditions are tested for in that state’s newborn screening programs. As of 2023, Pompe disease was a part of newborn screening programs in 45 U.S. states and Washington, D.C.
Pompe disease is a lifelong and progressive disorder, and its symptoms generally worsen over time. Disease symptoms often can cause difficulties with activities in day-to-day life — for example, most late-onset patients experience some difficulty walking, and many will eventually rely on a wheelchair to get around. Learning new coping strategies and finding accommodations can help make navigating daily life with Pompe disease less burdensome.
All forms of Pompe disease are life-limiting — the disease can cause problems with the heart muscle and muscles needed for breathing, leading to heart and respiratory failure. The specific prognostic outlook varies depending on a number of factors, including the disease type, specific disease-causing mutations, and treatments.
Related Articles
