Pompe disease is a rare genetic condition caused by mutations in the GAA gene, which contains the information necessary to produce the acid alpha-glucosidase enzyme. The lack of this enzyme causes a complex sugar molecule called glycogen to accumulate inside cells, damaging them and leading to symptoms that include muscle weakness, breathing problems, and eating difficulties.

GAA mutations result in either a complete lack of the enzyme or a reduction in its activity. Infants with no functional enzyme are most severely affected by Pompe disease, while those with sufficient levels of acid alpha-glucosidase may lead a symptom-free life for decades.

Diagnosing Pompe disease can be complicated, and it may take time for a definitive diagnosis to be reached. Typical symptoms, such as muscle weakness and heart disease, overlap with other illnesses. Moreover, early symptoms can be different for each patient and may appear at any age.

Physicians may also struggle to recognize Pompe because the disease is very rare.

But a number of tests exist to confirm Pompe disease in a person.

Differential diagnosis

Several signs and symptoms of Pompe disease, like poor muscle tone, an enlarged heart or frequent chest infections, are common to other conditions. A thorough and differential diagnosis can distinguish Pompe from diseases with similar symptoms. Specialists such as neurologists, cardiologists, geneticists, pediatricians, and general practitioners may be needed for a differential diagnosis.

If the differential diagnosis concludes that symptoms point to the possibility of Pompe disease, further testing is necessary for confirmation.

Enzyme activity tests

Upon suspicion of Pompe disease, the levels and activity of the acid alpha-glucosidase enzyme can be measured using different methods.

One minimally invasive way is checking for the enzyme’s presence through a skin biopsy. Skins cells are cultured to produce fibroblasts in the laboratory and then examined for enzyme levels. (In Pompe patients, these levels usually range from less than 1 percent to 40 percent.) Enzyme activity can also directly be measured on a muscle biopsy based on tissue pathology, but this is a more invasive approach.

Blood tests are another non-invasive way of determining the activity of acid alpha-glucosidase. Testing enzyme activity in white blood cells isolated from a blood sample is one such approach; a whole blood test is another. A blood spot test, where a blood sample from the patient is dried on a filter paper, is also an effective way of screening for Pompe disease.

Blood tests to measure enzyme activity is reported to be increasingly replacing biopsies, especially muscle biopsies, as a diagnostic approach, because of their fast and reliable results.

Genetic testing

While enzyme activity tests are the main diagnostic approaches when Pompe disease is suspected, genetic testing may also be requested.

DNA analysis, based on a sample of blood or spit, can examine the GAA gene to determine mutations in a patient.  Mutation analysis on a blood sample can confirm this diagnosis.

Because Pompe is an inherited disease, identifying family members who carry GAA mutations is important for the genetic counseling that can help them make informed decisions about family planning. Prenatal testing is also available for parents who are at a high risk of having a child with Pompe disease.

Additional tests

A specialist may ask for additional tests to complement and confirm previous test results. One symptom of classic infantile form of Pompe disease is cardiomyopathy, which can cause irreversible heart damage if not treated. Doctors may need to take a chest X-ray regularly to determine if heart is enlarged, an electrocardiogram (ECG, or EKG) to detect abnormal heartbeat patterns, and an echocardiogram (Echo) to make sure that the heart muscle is functioning properly.

Since muscle weakness is also a common symptom of Pompe disease, tests for creatine kinase (CK) measurements and an electromyogram (EMG) can also be used to assess the presence of muscle injury and dysfunction.

Respiratory problems that may disrupt sleep are also known to affect Pompe disease patients. Breathing tests and sleep studies can be performed to assess how well the lungs are working.

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