The challenge in diagnosing Pompe disease

Diagnosing Pompe disease can be difficult for several reasons.

Firstly, because the condition is so rare, many doctors have not encountered it before and so may not consider it as a possible diagnosis. In addition, many signs and symptoms of Pompe disease are not unique to it, so they can easily be confused with those of more common conditions. To make things even more complicated, Pompe disease can affect many parts of the body, with different people often affected in different ways.

Diagnosis can be complicated and may take some time. It may involve several different doctors and a variety of tests. Different tests may be used to help doctors narrow down the possible cause of a patient's symptoms. If Pompe disease is suspected, diagnosis can be made using blood tests. 

Tests that may be used in the process of diagnosing Pompe disease:

Tests to examine the heart

Tests to examine the heart are most important for infants with Pompe disease, who almost always have heart problems. X-rays and ultrasound may be used to examine heart size because the heart is often abnormally large in infants with this condition. Other tests may be carried out to examine the thickness of the heart muscle and the rhythm of heart beats. 

Muscle and movement tests

Muscle weakness can be determined by examining a person’s movements and assessing the difficulty that they have in performing certain tasks. With infants and children, it is also important to see whether they meet standard developmental milestones for their age, such as sitting up, crawling and walking.

Breathing tests

A range of tests can be used to measure how well a person’s lungs are working, which in turn indicates how well their breathing muscles are functioning. In addition, sleep studies (in which a person is observed and tested while sleeping) can identify breathing problems that occur whilst lying down. This is important, because such problems are common in Pompe disease.

Lab & blood tests

Abnormal levels of certain substances in the body can point to the possibility of Pompe disease. One of these substances is ‘creatine kinase’ (CK), which is seen in the body at unusually high levels when muscles are damaged. High CK levels are therefore seen in most people with Pompe disease, but they also occur in many other muscle disorders.

When doctors suspect a muscle problem, they may take a small sample of muscle tissue to view under a microscope. This is called performing a ‘muscle biopsy’. If build-up of glycogen is seen in these muscle cells, Pompe disease is confirmed. However, the part of the body that the biopsy is taken from is very important. That’s because glycogen doesn’t build-up equally or at the same rate in all muscles. So a biopsy from certain muscles may not show glycogen build-up, even if the person has Pompe disease.

Confirming the diagnosis

Measuring GAA 

All people with Pompe disease have a lower than normal amount of GAA enzyme, or even virtually none (see ‘What causes Pompe disease’ section). GAA is measured using a test called an ‘enzyme assay’. The amount of GAA in a person with Pompe disease can range from less than 1% of normal (usually found in infants) to up to around 30% of normal.   A GAA amount of less than 1% to 30% of normal therefore usually identifies Pompe disease. Doctors will usually use more than one test to confirm the diagnosis of Pompe disease. 

GAA testing can be performed on a variety of samples, such as blood, skin cells and muscle. Using blood has the following advantages:
•    Simple – may only need a few drops of blood
•    Fast – results usually available within just a few days, as opposed to several weeks with some other methods

Gene analysis

A blood test called ‘mutation analysis’ may also be used to confirm that a person has Pompe disease. Instead of measuring GAA, this method – also called ‘genotyping’ – uses a blood sample to see if a person has the gene defect that causes Pompe disease. This is especially useful within families, to identify carriers of Pompe disease, as carriers may have normal or near normal GAA levels (see ‘Inheriting Pompe disease’ section).