Late-onset Pompe disease

Last updated Nov. 7, 2024, by Susie Strachan
Fact-checked by Patrícia Silva, PhD

Adult-onset Pompe disease typically begins after 1 year of age through to adulthood, and the condition is then known as late-onset Pompe disease.

This type of Pompe is characterized by symptoms that include slowly progressive respiratory problems and skeletal muscle weakness. Generally, the earlier the disease is diagnosed in life, the more severe the symptoms.

There are three types of Pompe disease, first identified in 1932 by Dutch pathologist Johannes Cassianus Pompe. Along with late-onset Pompe disease are classic infantile Pompe disease, evident within a few months after birth, and the nonclassic infantile-onset form of Pompe disease. The nonclassic form sees symptoms arise during the first year of life, but typically later than in the classic form.

Causes of late-onset Pompe disease

Pompe disease, also known as glycogen storage disease type 2 (GSD2), is caused by mutations in the GAA gene, located on chromosome 17, that encodes the instructions for making acid alpha-glucosidase (GAA) enzyme. This enzyme is responsible for breaking down a complex sugar called glycogen. When the body needs energy, glycogen is then broken down into glucose, a simpler sugar molecule.

In people with Pompe disease, mutations 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; either way, glycogen cannot be broken down as it should be, and eventually builds up to toxic levels inside cells. Muscle cells are especially affected by this, as glycogen usually serves as a main source of energy in these cells, working to power muscle movements.

Those with late-onset Pompe disease can have enzyme activity levels 40% or less of what is considered normal. In comparison, infantile-onset Pompe patients typically have less than 1% of GAA enzyme activity, while those with nonclassic forms usually have less than 10%.

Pompe disease is inherited when a person receives two mutated copies of the GAA gene, one from each biological parent.

A person with only one mutated copy of the GAA gene is called a Pompe disease carrier. Such carriers will not develop the disease, but may pass the Pompe-causing mutation to their biological children.

The Pompe disease database lists hundreds of variants of the GAA gene.

Symptoms of late-onset Pompe disease

The progression of glycogen accumulation in a person with late-onset Pompe disease can cause clinical debilitation, organ and system failure, and loss of life.

Symptoms of late-onset Pompe disease can include:

• progressive muscle weakness
• skeletal issues, such as scoliosis and contractures, or the permanent tightening of muscles or other tissues
• respiratory muscle weakness
• difficulty eating
• digestive problems
• trouble hearing
• an enlarged heart.

Muscle weakness, particularly in the legs and torso, is a key indicator of late-onset Pompe disease. People with the condition may also experience exercise intolerance, weak limb muscles, and lower back pain. Children may have delayed motor development.

Those with Pompe also may develop a sideways curvature of the spine, known as scoliosis — a coexisting condition that may especially affect adolescents. People with late-onset Pompe disease may experience muscle cramps, as well as headaches and fatigue. Nearly half of people with late-onset Pompe disease report pain in at least one part of their body.

Potential cardiac system issues include an enlarged heart, known as cardiomegaly, and rhythm disturbances.

People with late-onset Pompe disease also may experience difficulty chewing, weight loss, and other digestive problems.

Other issues patients can experience include breathing difficulties, sleep apnea, dyspnea, and respiratory infections. Respiratory muscle weakness eventually will lead to respiratory failure over time, which is the leading cause of mortality for patients.

Some people also may experience hearing impairment.

Diagnosing late-onset Pompe disease

A definite diagnosis of late-onset Pompe disease typically requires enzyme activity tests and genetic testing. Enzyme activity tests look for reduced activity of the GAA enzyme, while genetic testing helps identify disease-causing mutations in the GAA gene.

Genetic screening may be offered to family members.

Muscle weakness, in particular, can be evaluated:

• by checking the levels of creatine kinase, which are elevated in Pompe disease patients
• via electromyography, a test of the electrical activity in muscles
• by evaluating a patient’s breathing ability through tests like spirometry, a measure of lung function.

Pompe disease can be difficult to diagnose, and can be mistaken for muscular dystrophy, spinal muscular atrophy, rigid spine syndrome, and myasthenia gravis, among others.

The earlier a person receives a late-onset Pompe disease diagnosis, the sooner treatment can begin.

More information on diagnosing the condition is available on the Pompe Disease News site.

Prognosis and treatment

The prognosis of late-onset Pompe disease depends on how early it is diagnosed. Generally, symptoms are less severe when the disease is diagnosed later in life.

Life expectancy for people with late-onset Pompe disease can range from early childhood to late adulthood. This is affected by the progression of the disease, respiratory issues, and other comorbidities, or co-occurring conditions.

Two enzyme replacement therapies (ERTs) are available in the U.S. for use as a late-onset Pompe disease treatment:

• Lumizyme (alglucosidase alfa), also known as Myozyme outside of the U.S.
• Nexviazyme (avalglucosidase alfa), approved to treat late-onset Pompe disease in patients ages 1 and older.

Treatment with ERT has been shown to extend life expectancy for people with Pompe disease and improve their quality of life. However, ERT is not a cure for late-onset Pompe disease.

A combination therapy of Pombiliti (cipaglucosidase alfa) + Opfolda (miglustat) has also been approved for certain adults with late-onset Pompe disease. Cipaglucosidase alfa (Pombiliti) is a form of the GAA enzyme, and miglustat (Opfolda) is an enzyme stabilizer. This combination approach works mainly to improve walking ability and at least stabilize respiratory function.

Supplemental treatments

Along with getting approved medications, having a multidisciplinary team can allow patients to be treated for the pulmonary, neuromuscular, orthopedic, and gastrointestinal symptoms of late-onset Pompe disease.

Some of these treatment approaches for late-onset Pompe disease include:

• physical and occupational therapy to preserve motor function and assess the risk of falling
• exercise, after being assessed by a cardiologist and pulmonologist
• speech therapy to help with communication
• nutritional support for a good diet, comprising 25% to 30% caloric intake of protein
• respiratory therapy
• orthotics to assist with posture and prevent contractures
• assistive devices for mobility, breathing, communication, and feeding.

Physiotherapy also can include stretching exercises to slow contractures, and patients can set up an exercise plan that may include walking, using a treadmill, biking, swimming, doing submaximal aerobic exercise, or muscle strengthening.

A number of experimental therapies are also being explored in Pompe, including clinical trials looking at gene therapy.

A number of international organizations offer support groups for people with late-onset Pompe disease and their families. Among them are the Acid Maltase Deficiency Association and the United Pompe Foundation.

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.