Pompe disease diagnosis
Last updated Nov. 4, 2024, by Marisa Wexler, MS
Fact-checked by José Lopes, PhD
A diagnosis of Pompe disease typically requires testing the activity of the acid alpha-glucosidase enzyme as a first-line method. This enzyme normally breaks down a complex sugar molecule called glycogen. People with Pompe disease have a deficiency in functional alpha-glucosidase, resulting in glycogen accumulation inside cells, especially muscle cells, damaging them.
To confirm a diagnosis of the rare genetic disorder, the general recommendation is to conduct genetic testing looking for mutations in the GAA gene, the cause of Pompe disease, which codes for the alpha-glucosidase enzyme.
Several other tests may help in establishing a Pompe disease diagnosis, such as assessments of heart structure and function, muscle health, and markers of liver damage and glycogen buildup. Some people with Pompe may experience an enlarged liver.
However, diagnosing Pompe disease can be complicated, and it usually takes some time for a definitive diagnosis to be reached. That’s in part because the typical Pompe disease symptoms, such as progressive muscle weakness and heart disease, are also found in other conditions. In addition, early Pompe symptoms can be different for each patient, and may appear at any age.
Further complicating matters, because Pompe disease is rare, healthcare providers may struggle to recognize the condition.
What tests are used to diagnose Pompe disease?
The main tests used to diagnose Pompe involve looking for reduced activity in the acid alpha-glucosidase enzyme or identifying disease-causing mutations in the GAA gene. It is generally recommended that, when feasible, both enzyme activity tests and genetic testing should be done to confirm the Pompe disease diagnosis.
Enzyme activity tests
An enzyme activity test generally is done using a sample of a person’s cells. Tests may be done on cells taken from a muscle or skin biopsy — though in recent years, it has become increasingly common to do enzyme tests using a blood sample. In particular, a dried blood spot or DBS, where the blood sample is dried on a filter paper, can be used to look for Pompe disease, especially in newborn screening.
In Pompe disease, testing can be done to measure the activity of the acid alpha-glucosidase enzyme; this can vary depending on the disease type. Typically, individuals with infantile-onset Pompe disease have enzyme activity that is less than 1% of normal, while those with late-onset disease have enzyme activity levels up to 40% of normal.
Genetic testing
The aim of genetic testing is to identify disease-causing mutations in the GAA gene. This often is done with a sample of blood or saliva. A number of different technologies may be used in genetic testing: Some test only for specific, known, disease-causing mutations, while others determine the entire sequence of the GAA gene.
Because Pompe is an inherited disease, assessing family history to identify relatives who carry GAA mutations is important, as it can allow for genetic counseling. Such counseling can help family members to make informed decisions about family planning. Prenatal testing, done during pregnancy, also is available for expectant parents who are at a high risk of having a child with Pompe disease.
Other tests
While enzyme activity and genetic testing are the gold standards for making a definitive diagnosis of Pompe, a number of other tests may be used in the diagnostic workup.
Babies with classic infantile-onset Pompe disease exhibit a form of heart muscle damage called cardiomyopathy. Tests to check for heart damage may include:
- chest X-rays to determine if the heart is enlarged — a sign of heart damage
- an electrocardiogram (EKG or ECG) to detect abnormal heartbeat patterns
- an echocardiogram, known as an Echo, to test whether the heart muscle is functioning properly.
As Pompe mainly affects muscles, assessments of muscle function are commonly used in the diagnosis and management of the disease. Among such tests are:
- a muscle MRI to track muscle degeneration
- an electromyogram to detect alterations in muscles’ electrical activity.
Several nonspecific laboratory tests may show abnormalities in individuals with Pompe, including:
- elevated levels of creatine kinase (CK) and/or lactate dehydrogenase in blood, both markers of muscle damage
- higher than normal levels of aspartate (AST) and alanine (ALT) aminotransferase, markers of liver damage in blood
- increased tetrasaccharide 6-alpha-D-glucopyranosyl-maltotriose (Glc4) in urine, an indicator of glycogen storage disorders
- glycogen buildup visible in microscopy of cells.
Those with Pompe disease may experience breathing difficulties due to weakness in the muscles needed for respiration, and such difficulties can cause sleep problems. Breathing tests and sleep studies help to assess these complications.
Who diagnoses Pompe disease?
A variety of specialists, including neurologists, cardiologists, geneticists, and pediatricians, all may be involved in diagnosing Pompe disease. A patient’s general practitioner may be involved as well.
Many of the hallmark signs and symptoms of Pompe disease, such as poor muscle tone, an enlarged heart, and/or frequent chest infections, are found in other conditions. Thus, a thorough evaluation is needed to distinguish between Pompe and other disorders. That process is called a differential diagnosis.
How long can Pompe disease go undiagnosed?
Babies with classic infantile-onset Pompe disease usually show symptoms, and often marked abnormalities, within the first few months of life. However, individuals with late-onset Pompe may not develop any noticeable symptoms until adulthood. Therefore, it is possible for someone with Pompe to go decades without being diagnosed.
Even once symptoms do become apparent, most patients with Pompe experience a substantial diagnostic lag, which in turn delays the start of treatment. Generally, a delayed diagnosis is tied to poorer clinical outcomes.
Among babies with classic infantile-onset disease, a median diagnostic delay of more than a month has been reported. For late-onset patients who don’t develop symptoms until after age 12, the median delay is reported to be about six years. Diagnostic delays of more than a decade also have been reported.
| Test | Purpose |
|---|---|
| Enzyme tests | Used to measure activity of the acid alpha-glucosidase enzyme whose deficit causes Pompe disease |
| Genetic testing | Used to identify Pompe disease-causing mutations in the GAA gene |
| Other tests | Nonspecific tests used to identify and monitor Pompe disease signs and symptoms, which may include:
|
What should people expect after a diagnosis of Pompe?
After being diagnosed with Pompe disease, patients and their healthcare providers should work together to come up with a treatment plan.
The current standard of care is enzyme replacement therapy, or ERT, which involves giving the patient a working version of the acid alpha-glucosidase enzyme. ERT has been demonstrated to slow the progression of Pompe disease, helping to maintain muscle function and improve patients’ quality of life. It is recommended that patients start on ERT as soon as possible after a diagnosis is made.
Pompe is a lifelong and progressive disorder, meaning that the symptoms generally get worse over time. Patients usually receive continual monitoring. Supportive treatments may be given to help manage specific disease symptoms, and alterations in diet or exercise regimens may be recommended. All forms of Pompe are life-limiting, though survival outcomes are improving with recent advances in treatment.
Across the Pompe Disease News website, information, support, and resources are available for those living with Pompe. This includes learning from the experiences of other patients through our columns.
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 diagnosis
An enzyme activity test that looks for reduced activity of the acid alpha-glucosidase enzyme is usually the first-line method to definitively diagnose Pompe. Genetic testing to detect disease-causing mutations in the GAA gene also may help confirm the diagnosis. It often is recommended that both enzyme activity and genetic testing be performed to confirm the diagnosis, if possible.
Depending on the disease type, Pompe may cause noticeable abnormalities shortly after birth, or it may not cause any detectable symptoms until later in childhood or adulthood. The median age at diagnosis for children with infantile-onset disease is about four months. In late-onset disease, meanwhile, the median age at diagnosis has been reported at 38 years. Notably, most people with Pompe disease experience a substantial delay between the initial onset of symptoms and the eventual diagnosis of the disorder.
The mutations that cause Pompe are inherited from a person’s biological parents; they are present in a developing fetus from the moment of conception. As such, it is possible to do genetic testing to check for Pompe disease before a fetus is born, referred to as prenatal testing.
Yes. Prenatal genetic testing can be done to detect Pompe disease in a developing fetus before birth.
No. Often when people show signs of a disorder affecting their muscles, clinicians will take a muscle biopsy for analysis as part of the early diagnostic workup. While many individuals with Pompe do show characteristic abnormalities on a muscle biopsy, there is a lot of variability in how muscles are affected, even within the same individual. Consequently, false-negative results from muscle biopsy can occur, particularly in individuals with late-onset Pompe disease.
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