What Medical Tests Are Used to Diagnose and Monitor Pompe Disease?

A number of tests may be done to help diagnose Pompe disease and determine the extent of muscle weakness or how far the disease has progressed. However, an enzyme assay is commonly used to confirm a diagnosis of Pompe disease. The enzyme assay may be performed in different ways. This biochemical test measures the activity of acid alpha-glucosidase in a small sample of skin, muscle, or blood.

Enzyme Assay Testing

Enzyme Assay Test

The definitive method of diagnosing Pompe disease is an enzyme assay test performed on a sample of blood, skin, or muscle tissue. In this procedure, physicians send the sample to a laboratory for enzyme activity analysis.

Before a muscle or skin tissue sample is taken, patients are given a local or general anesthetic so that there is minimal to no discomfort, although the area may be sore afterwards while it heals. Although either muscle or skin tissue can be used to diagnose Pompe disease, skin biopsies may be preferred because they are not generally as invasive as muscle biopsies.

To confirm whether a patient has Pompe disease, enzyme activity testing is performed on the tissue sample to determine the activity of acid alpha-glucosidase (GAA). If the patient’s GAA activity is low or undetectable, a conclusive diagnosis can be made.

Most late-onset patients with Pompe disease have less than 40% of normal GAA activity levels base on cultured skin fibroblast samples
In some infantile-onset patients, skin and muscle biopsies have demonstrated undetectable levels of GAA enzyme

Using Blood Samples for Enzyme Assay

Using a blood sample, the GAA enzyme activity levels can be measured in lymphocytes as a way to find acid alpha-glucosidase activity levels. In patients with Pompe disease, these levels are low.

Using Dried Blood Spots for Enzyme Assay

Efforts are underway to develop noninvasive tests that can detect acid alpha-glucosidase in a dried-blood spot. Once available, these tests will provide a simpler, less expensive, and faster way to screen for Pompe disease in larger numbers of patients and will make it easier to screen newborns who cannot tolerate invasive tests that require surgery or anesthesia.

Genotype Testing

Known Pompe mutations can be identified using genotype testing, which examines the DNA in a blood sample. This is sometimes done when Pompe disease is suspected or when a presumed diagnosis has been made but not confirmed, and may also be done when there is a family history of Pompe disease.

Other Assessments

In the course of diagnosing Pompe disease, health care providers may also order other tests to assess a patient’s current status and provide the physician key data from which to make a diagnosis. These tests may point toward a muscle disorder as a likely diagnosis or detect which muscles and organs may be affected and to what extent. These tests may include:

Creatine kinase blood tests to check the level of creatine kinase (CK), an enzyme that is released at higher levels when muscle injury occurs
Electromyography (ee-lek-TRO-my-AH-graph-ee) (EMG) , a test that records electrical activity in affected muscles (but may show a normal pattern in some people with late-onset Pompe disease)
A chest x-ray, often performed in infants to see if the heart is enlarged
An echocardiogram (eh-co-CAR-dee-oh-gram) or echo test, an ultrasound that can show if the heart muscle has become too thick or is not functioning properly
An electrocardiogram (EKG) that can detect abnormal patterns of heartbeats and electrical activity

To learn more about some of these tests, read the sections below.

Creatine Kinase Blood Tests

A blood test may be ordered as an early step in the diagnostic process because a good deal of information can come from a blood sample. Specifically, the physician may ask the laboratory to examine the levels of a particular enzyme called creatine kinase (CK).

Research has shown that more than 90% of patients with Pompe disease display increased levels of this enzyme, which the body releases in greater quantities when muscle injury occurs. As a result, an elevated CK level helps to focus the diagnosis inquiry on a muscle disorder. Because there are many muscle disorders, however, more specific tests are required to narrow the diagnosis to Pompe disease.

Liver Enzyme Blood Tests

In patients who have an enlarged liver, or who are undergoing a general diagnostic workup, physicians may also order a test that determines the levels of various liver enzymes in the blood. Pompe patients often demonstrate increased levels of certain enzymes, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

Electromyography (EMG)

Electromyography is often used in the diagnosis of neuromuscular disorders. When you have an EMG, the technician places an electrode through the skin and into the muscle in order to create an audio or video record of the electrical activity of the selected muscle. In Pompe disease, an EMG exam generally reveals patterns that would indicate a muscle disease, although some muscles may appear normal in late-onset patients.

Radiology (x-ray)

A simple chest x-ray is a noninvasive way to diagnose heart involvement. This is often done in infants. This may reveal an enlarged heart, which can lead a physician to perform further tests. For example, a physician may recommend an echocardiogram and electrocardiogram as described below.

Echocardiography (“Echo”) and Electrocardiography (ECG)

Echocardiography and electrocardiography are two tests used to evaluate the heart. The physician may order one or both of these procedures for infantile-onset patients to find out how well the heart is working and whether the heart has been affected by Pompe disease.

Both can help physicians find out whether a young patient has infantile-onset or late-onset Pompe disease, since the presence of heart problems may help distinguish between the two types. Infantile-onset patients typically show a markedly enlarged heart while late-onset patients rarely have heart symptoms.

Echocardiography, or “echo” test, is an ultrasound procedure in which sound waves are bounced off the heart to create images of the chambers and valves. This test can show heart enlargement, abnormal heart muscle thickness, and the deficiency of the heart’s pumping motion.

Electrocardiography (ECG) examinations involve the placement of electrodes on the chest to record heart rhythm, heartbeat frequency, and electrical activity. Infants with Pompe disease generally show abnormal patterns on an ECG exam.