Pompe disease is a neuromuscular condition that mostly affects skeletal and respiratory muscles. The condition happens when the body doesn’t have enough of an enzyme called acid alpha-glucosidase (GAA). Clinical symptoms and severity of Pompe disease can be different for each person and can be considered as a spectrum.

Pompe disease is a type of glycogen storage disease (GSD) that also affects lysosomes, parts of cells that help break down substances. It’s also known as glycogen storage disease type II (GSDII or GSD2). It may also be called acid maltase deficiency (AMD).

There are two forms of Pompe disease:

• Early onset infantile/child Pompe disease (IOPD) – this form occurs when the body has little to no GAA, and symptoms can appear in the first few months of life.
• Late onset juvenile/adult Pompe disease (LOPD) – this form occurs when the body has low levels of GAA, and symptoms can appear from childhood through to late adulthood.

Early onset infantile Pompe disease (IOPD)

Symptoms of early onset Pompe disease usually begin in the first few months of life and are often severe. Infants typically present with low muscle tone (hypotonia), rapidly progressing generalised muscle weakness, and difficulties with feeding that can lead to problems gaining weight and slow growth. An enlarged heart (hypertrophic cardiomyopathy) is common, and respiratory problems may also occur as the disease affects the muscles involved in breathing.

Respiratory problems can include frequent respiratory infections, shortness of breath, and respiratory failure – which can be life-threatening if left untreated. Many infants also have an enlarged tongue. Other signs may include delays reaching motor milestones, such as rolling over or walking, and, in some cases, changes in bone structure might develop due to muscle weakness.

Early treatment using enzyme replacement therapy (ERT) has improved the prognosis (likely outcome) for infants with IOPD and can help with heart disease, muscle strength, and respiratory function. However, the effectiveness of treatment can vary, and early intervention is crucial. Without treatment, infants with IOPD do not usually survive beyond the age of two. ERT does not cure Pompe disease, and children are still likely to experience significant health challenges, but it can improve quality of life.

Late onset juvenile/adult Pompe disease (LOPD)

Symptoms of late onset Pompe disease vary widely in severity and may not appear until childhood, adolescence, or even adulthood. Progressive muscle weakness is common and typically starts in muscles near the body’s core, such as the hips, shoulders, and torso, before spreading to other muscles. This can make some activities more difficult, like climbing stairs, lifting objects, and performing daily tasks. Weakness in the breathing muscles can also cause respiratory issues to develop. Over time, some people may experience severe respiratory problems that require non-invasive ventilatory (NIV) support. Unlike the infantile form, heart disease is rare, but some people may experience other heart-related issues, such as abnormal rhythms.

Genetic changes

Pompe disease is caused by changes in the GAA gene, which makes the enzyme acid alpha-glucosidase (GAA). This enzyme breaks down glycogen into glucose in lysosomes – small parts of cells that help break down waste and other substances. In Pompe disease, the GAA enzyme is missing or not working properly, so glycogen builds up in muscle cells because it’s not adequately broken down into glucose. The buildup causes damage, which results in muscle weakness.

Inheritance

Pompe disease is inherited in an autosomal recessive pattern. This means a person with Pompe disease will have inherited two copies of the changed gene, usually one from each parent.

For more information, see our inheritance and genetics page.

A diagnosis of Pompe disease typically starts with a referral from a GP to a neurologist or a metabolic specialist who will assess symptoms and recommend appropriate tests. A neurologist is a doctor who specialises in the muscles and nervous system and a metabolic specialist focuses on disorders related to metabolism and energy production.

A dried blood spot test can suggest the possibility of Pompe disease by measuring the activity of the GAA enzyme. A blood sample test (from a vein) can further measure GAA enzyme activity and creatine kinase (CK) levels. Elevated CK levels and low or no GAA activity suggest Pompe disease. Genetic testing can identify changes in the GAA gene and confirm the diagnosis. An MRI scan of the muscles may also be used to see how different muscle groups are affected, and to help with the diagnosis.

For more information, see our diagnosis page.

A multi-disciplinary approach is important in not only managing the condition and symptoms but in improving wellbeing too. It involves different healthcare professionals working together.

Access to a healthcare team

People with Pompe disease should have access to a multi-disciplinary healthcare team to manage symptoms and treatments. Usually, the lead professional will be a metabolic specialist or a neurologist, and the team may also include cardiologists, respiratory specialists, physiotherapists, speech and language therapists, and dietitians. If you don’t have contact with a specialist doctor, speak to your GP about getting access.

Pompe disease is progressive and may require regular assessments of heart, breathing, and swallowing functions. Mobility support and respiratory care are key in long-term management of the condition.

Treatments

Disease-modifying treatments are available for Pompe disease, with enzyme replacement therapy (ERT) being the most common. ERT provides an artificial version of the GAA enzyme, which the body lacks in Pompe disease. It’s given through an intravenous (IV) infusion, typically every two weeks. ERT helps reduce the buildup of glycogen in the muscles and slows disease progression. While its effectiveness can vary, it may improve muscle strength and motor function. When used in children with IOPD, ERT has significantly improved survival rates.

Myozyme, the first ERT available, is used for both IOPD and LOPD. Recently approved treatments in the UK include Nexviazyme (avalglucosidase alfa), which is used for both IOPD and LOPD, and Pombiliti (cipaglucosidase alfa), a combination of ERT and oral medication, which is only approved for LOPD in people aged 18 or over. At Muscular Dystrophy UK, we play a key role in the appraisals of these new treatments, often acting as a formal Patient Expert. For more information, visit our access to treatments page.

Respiratory

Breathing problems are a major concern in Pompe disease, for both early onset and late onset cases. Regular lung function monitoring and overnight sleep studies are essential. Non-invasive ventilation (NIV) may be recommended to support breathing – particularly during sleep. Cough assist devices and respiratory physiotherapy can help manage respiratory weakness and clear the airways.

Exercise and diet

Staying aerobically fit is one of the best ways to help muscles perform better and improve quality of life. A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can put together a suitable exercise plan to follow. It’s recommended to exercise at below 70% of a person’s maximum capacity. This means aiming for a level of effort that is challenging but not overwhelming, helping to prevent overexertion and reduce the risk of injury. Walking, swimming, or cycling are examples of suitable aerobic exercise. It’s important to stop exercising and rest if experiencing muscle pain or fatigue. Healthy eating and maintaining a healthy body weight is also important. To find out more about advice for adults, see exercising with a muscle wasting condition.

Anaesthesia stops a person feeling pain during a procedure or surgery. People with Pompe disease are at risk of anaesthesia-related complications because of respiratory problems, and cardiovascular problems in those whose heart is also affected. It’s important to inform the anaesthetist and surgical team of the Pompe disease diagnosis, as they may need to consult specialists for safe management. A thorough preoperative assessment is essential, along with careful monitoring during and after surgery for an extended period. Non-invasive ventilation (NIV) may be necessary during and after surgery to support breathing.