Pompe disease

Newborn screening is performed for several genetic conditions in the United States, and the conditions screened for are determined on a state by state basis. The Secretary of Health and Human Services makes recommendations for what diseases should be put on the newborn screen, but individual states have the final say in what is added. The Secretary of Health and Human Services recommended Pompe disease to be added to NBS in March of 2015. As of December 2015, there are 3 states that are performing newborn screening (NBS) for Pompe disease. In 2013, Missouri was the first state to start NBS for Pompe. Now Illinois and New York have started NBS, and other states will follow soon. There are also several states including Georgia and Wisconsin which will be doing pilot projects in their state for one year beginning in the summer of 2016.

Taiwan was the first country to provide newborn screening for Pompe disease and found a higher incidence than previously recorded.

There are several ways to get tested for Pompe disease. For babies born in certain countries, including some states in the United States (Missouri, New York, and Illinois), newborn screening (NBS) may look for Pompe disease. This means that every baby is being screened while they are in the hospital, right after being born, for many diseases including Pompe disease. While NBS will find many babies with Pompe disease, it can miss some babies and other babies will screen "positive" even though they don't have Pompe disease. When a baby screens "positive", further testing needs to be done to find out if the baby does or does not have Pompe disease.

If a baby, child, or adult has symptoms of Pompe disease, testing usually starts with a blood test looking at the GAA enzyme level. If the enzyme level is low, this is often enough for a diagnosis. However, the doctor may also do a blood test (called sequencing) looking at the code of the GAA gene (the gene that causes Pompe disease when it doesn't work). The sequencing test looks for changes in the code of the gene that cause the gene not to work correctly. People with Pompe disease have two changes in this gene, one on the copy they inherited from their mother and one on the copy they inherited from their father.

Lastly, if a person has muscle weakness and the doctor wants to test for many causes of muscle weakness at the same time, the doctor can order a sequencing panel test. The panel test is also a blood test, but tests for 30-40 (or more) genes that, when they have changes, are known to lead to muscle weakness. It is often faster and cheaper to do a panel test if the cause of muscle weakness is unknown rather than to test one gene at a time. In March of 2015, the Muscular Dystrophy Association and other partners joined together to offer free testing for limb girdle muscular dystrophy for qualifying patients. More information is available to medical professionals and patients here: https://www.lgmd-diagnosis.org/

For more information about genetic testing options, including panel testing, go to GeneTests.org.

More information: NBS for Pompe.

While Pompe disease is relatively rare, it can run in families and be passed from parents to children. The way that Pompe disease is passed down is called autosomal recessive inheritance. This means that in order to develop symptoms of Pompe, a person must have inherited two non-working copies of the GAA gene, which is the gene associated with Pompe disease. If a person has one working copy and one non-working copy, they are a carrier for Pompe disease but do not have any symptoms themselves. We assume that both parents of an affected person are carriers, so each of their children has a 1 in 4 or 25% chance of having Pompe disease as well. Testing the brothers and sisters of someone who has Pompe disease is important because it can find out who is a carrier and who is also affected by Pompe disease (but may not have visible symptoms yet). The aunts and uncles of people with Pompe disease may also be carriers. If other people in the family want to know their chances to have a baby with Pompe disease, they can be tested for the same gene changes as the person diagnosed with Pompe disease.

In Pompe disease, the alpha-glucosidase enzyme, also known as acid maltase, is not working properly. Testing for the enzyme level is best performed in a blood sample. Genetic testing can sometimes be done on a saliva sample, but there is a possibility of not being able to get enough DNA, or genetic information, from the saliva sample to do the testing, especially for multiple gene panel testing. Sometimes when a person has muscle weakness, a muscle biopsy (a small piece of muscle is taken) will be done to look at the muscle for changes that would tell the doctor a reason for the weakness. In Pompe disease, the muscle biopsy will usually show glycogen storage. However, sometimes the muscle biopsy is normal in people with Pompe. Therefore, it is important to do enzyme testing or genetic testing in someone with possible Pompe disease even if they had a normal muscle biopsy.

For more information about genetic testing options, including panel testing, go to GeneTests.org.

Creatine kinase (CK) is an enzyme that is produced in all muscles. When muscles are being broken down because of a muscle disease, the CK goes into the blood stream. Therefore, measuring CK in the blood can be an indication of whether a person has muscle breakdown. Around 95% of the time, a person with Pompe disease has elevated creatine kinase (CK/CPK) levels. Babies with infantile Pompe disease have very elevated CK levels because their muscles breakdown faster.

CK can be high for many reasons. If a person runs a marathon, they will likely have a high CK for a little while afterward because they had some mild muscle breakdown by running so long. However, if a person has a high CK without exercising and has some muscle weakness, it may be because of a muscle disease. In Pompe disease, the CK is elevated due to muscle breakdown and can be over 10 times the normal range (less than 200 UI/L).