Pompe disease

There is one FDA approved treatment for Pompe disease in the United States with a drug called Alglucosidase Alfa (Trade Name: Lumizyme). Lumizyme is an enzyme replacement therapy (ERT) which is a man-made enzyme that is infused into the vein of a person with Pompe disease every two weeks. The man-made enzyme can break down built up glycogen in the muscles. It is important to start ERT as soon as possible when someone is diagnosed with Pompe disease, because muscle that is too damaged by glycogen may not be able to be helped. Lumizyme is better at clearing out glycogen storage in the heart muscles compared with the skeletal muscles (muscles which help the body move).

In addition to ERT for Pompe disease, it is important to follow up regularly with several different medical specialists to manage different symptoms or possible symptoms of Pompe. First, it is recommended that everyone with Pompe disease be followed by a doctor who is knowledgeable about lysosomal storage diseases and/or Pompe disease. This may be a medical geneticist (genetics doctor), a neurologist (nerve doctor) in a Muscular Dystrophy Association clinic, or other doctor who has followed similar patients. Anyone with Pompe disease should follow regularly with a cardiologist (heart doctor) who may recommend an echocardiogram (ultrasound of the heart) and/or electrocardiogram (ECG; study of the heartbeat). A pulmonologist (lung/breathing doctor), gastroenterologist (GI; doctor for eating and swallowing issues), or an orthopedic surgeon (bone doctor) may also be needed depending on the symptoms. Regular physical, occupational, and speech therapy can be very helpful in helping to keep the muscles working longer.

Aside from medical management, an important first step after an initial diagnosis of Pompe disease is to get in touch with a support group that can provide the emotional support and resources that a newly diagnosed individual and their family may need.

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.

Pompe disease can be abbreviated as PD and this includes the forms of Pompe disease in infants as well as Pompe disease in children and adults. It may sometimes be abbreviated based on whether symptoms start in newborns (Infantile Onset Pompe Disease or IOPD) or after one year of age (Late Onset Pompe Disease or LOPD). Symptoms are usually different in IOPD than in LOPD. In IOPD, babies are born with very little muscle function and large hearts that do not work as well as they should (cardiomyopathy) because of excess glycogen in the muscle tissue. In LOPD, symptoms include muscle weakness that gets worse over time and breathing problems, but usually there is no cardiomyopathy. As the initials "PD" can stand for many different diseases, always look for a sentence that says Pompe disease is being shortened to PD when reading articles, webpages, or other documents.

Pompe disease, also known as acid maltase deficiency and glycogen storage disease type II, is a glycogen storage disorder that is caused by a specific gene called GAA not working correctly. Normally, GAA makes an enzyme called acid alpha-glucosidase. This enzyme breaks down glycogen in certain parts of cells called the lysosomes. Pompe disease is part of a larger group of about 50 conditions called lysosomal storage diseases, which all involve the lysosome not working properly.

Glycogen is a type of carbohydrate, or nutrient, that needs to be broken down into a smaller form for our bodies to use. When GAA doesn’t work, it can’t make acid maltase and glycogen builds up in the cells instead of being broken down. Excess glycogen damages cells and causes progressive muscle weakness (myopathy), including the muscles needed for the body to move (skeletal muscle), the heart to pump (cardiac muscle), and the lungs to breathe (respiratory muscle). The symptoms of Pompe disease can start as early as the newborn period or even before birth, but some types can start to show years later. In general, the earlier that symptoms start to show, the faster the disease progresses. Babies who have symptoms of Pompe disease are born with very low muscle function and large hearts that have trouble pumping blood. When a little enzyme is made by the body, the symptoms start later in life and usually don’t involve the heart. There is a treatment for both the severe and milder types of Pompe disease called enzyme replacement therapy, in which a man-made version of acid alpha- glucosidase is given every two weeks to break down the extra glycogen.

Babies with Pompe disease are often diagnosed based upon the symptoms seen at birth, but later onset Pompe disease may be more difficult to diagnose and require the involvement of multiple doctors who specialize in areas such as neurology (the nervous system) and metabolics (how the body turns food into energy). The best person to help figure out if someone has Pompe disease is your main doctor, who can then order testing or make referrals to the appropriate specialists.

In Pompe disease (PD), a person has a change on both copies of their GAA gene. If both changes are severe, then their GAA genes are unable to make any normal acid maltase enzyme. A test of the skin (and possibly a blood test) can look at Cross Reactive Immunological Material (CRIM). If a person is CRIM positive, they make a little bit of acid maltase enzyme, whereas someone who is CRIM negative makes no acid maltase enzyme. This is important because when we replace the missing acid maltase enzyme with a man-made version called alglucosidase alfa or Lumizyme® in a person with no natural acid maltase enzyme, the body may recognize it as a foreign substance and develop antibodies to fight off the enzyme. When that happens, the body breaks down the enzyme before it can work to clear glycogen and makes the enzyme useless. However, there are now some medications that can be given to lower the immune response to Lumizyme and help it work better. Therefore, it is important to test babies with infantile Pompe disease to determine if they are CRIM positive (likely to respond well to treatment) or CRIM negative (likely to develop antibodies to treatment) before starting treatment. Everyone with late onset Pompe disease (LOPD) is CRIM positive because they have to have some natural enzyme to have developed symptoms later in life.

Creatine kinase (CK) is an enzyme that is produced in all muscles. When muscles are being broken down because of a muscle disease, CK goes into the blood stream. Therefore, measuring CK in the blood can be an indication of whether a person has muscle breakdown. 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). People with late onset Pompe disease (LOPD) can have normal CK, but around 95% of the time it is elevated. It is important to remember that CK can be elevated for many reasons other than Pompe disease (it can be a measure of a heart attack because the heart muscle is breaking down, for example).

Assistive technologies are devices used to help someone with disabilities to be able to function in their daily life. In the bathroom, a shower chair, bathtub grab bar, or raised toilet seat may be helpful. Seat cushions can be helpful for sitting in a wheelchair, and a stand-up chair can help you get out of a chair. A hospital bed that moves up and down can help a person get in and out of bed independently. A ramp to the front door and wheelchair accessible doorways and rooms may be necessary. These modifications can allow you to live independently for longer or ease the burden on caregivers.

The health problems associated with Pompe disease include profound muscle weakness and breathing problems. In infantile (severe) Pompe disease, babies also develop a very big, weak heart which is a condition called cardiomyopathy. In late onset Pompe disease (LOPD), the heart is usually not involved, but the muscles the body uses to help the lungs move air in and out of the body (the diaphragm) becomes weak. Adults may find that it’s difficult to get out of a sitting position to a standing position without having to walk up the legs with the hands.

Without treatment, these symptoms get worse, causing problems with walking, sleeping, swallowing, and breathing. Intelligence is not usually affected by Pompe disease, meaning that people who have Pompe disease do not usually have any learning problems. Individuals with Pompe disease may also experience difficulty chewing, have muscle pain, and get respiratory tract (the lungs and airways) infections.

Babies with Pompe disease are often diagnosed based upon the symptoms seen at birth, but later onset Pompe disease may be more difficult to diagnose and require the involvement of multiple doctors who specialize in areas such as neurology (the nervous system) and metabolics (how the body turns food into energy). The best person to help figure out if someone has Pompe disease is their main doctor, who can then order testing or make referrals to the appropriate specialists.

When both copies of the GAA gene don’t work correctly, the alpha-glucosidase or acid maltase enzyme cannot be made. Acid maltase is important for breaking down glycogen in certain compartments in muscle cells caused lysosomes, which are the "recycling center" of the cells. Without acid maltase, glycogen builds up in the lysosomes and causes damage to muscle cells. When enough muscle cells are damaged, the person with Pompe disease develops muscle weakness in the muscles needed for the body to move (skeletal muscles), the heart to pump (cardiac muscles), and the lungs to breathe (respiratory muscles).

Pompe disease is caused by a change (also called a mutation or a variant) in the GAA gene which causes the gene to not work correctly. The GAA gene carries the instructions for making the alpha-glucosidase enzyme, also called acid maltase, which is important for breaking down glycogen in the body. We normally have two working copies of GAA in our cells and we inherit one copy from our biological mother and the other from our biological father. In order to develop symptoms of Pompe disease, both copies of GAA are not working properly. This is also called autosomal recessive inheritance, which means that both parents of someone with Pompe disease are carriers of one working and one non-working copy of the GAA gene. Since each parent has one working copy, they don’t have symptoms of Pompe disease themselves. However, when they have children, they each have a 1 in 2 or 50% chance of passing on the non-working copy to their child. When both parents are carriers, there is a 1 in 4 or 25% chance of both of them passing on the non-working copy and having a child with Pompe disease.

People have around 20,000 genes in every cell of our bodies. Almost all of our genes come in pairs. We get one copy of each gene from our mother in the egg cell and the other copy from our father in the sperm cell. Pompe disease is caused by having two non-working copies of the GAA gene. When a person has a non-working copy of a gene, it is due to a change in that gene and may also be called a mutation. A person with one working GAA gene and a mutation in their other gene are called carriers. Carriers do not have any symptoms of Pompe disease because they still have one working copy of the gene. They usually inherited the mutation from either their mother or their father, and they can pass on either the mutation or the working copy to each of their children. There is a 50% chance of passing on the mutation or non-working gene to each child.

There are several things to consider when thinking about going on enzyme replacement therapy (ERT) for late onset Pompe disease (LOPD). Currently, there is only one FDA approved medication for Pompe disease: alglucosidase alfa (Lumizyme®) made by Sanofi Genzyme. Lumizyme has been shown to be effective at reducing glycogen stores in the heart muscles (cardiac muscle) but works less well in the skeletal muscle because skeletal muscles do not have as many receptors to take up the enzyme. (Think of it like buckets needed to take water from a river to bring it in the house. Without the buckets, you can’t get the water from the river to the house. Cardiac muscle has lots of buckets, while skeletal muscle has less). Still, it slows progression of the disease even in the skeletal muscle so that people with LOPD can use their muscles longer.

ERT is very expensive, but health insurance usually covers most of the cost of ERT. Many times, the remaining cost of ERT can be covered by co-pay assistance programs. The ERT infusions take several hours and must be done every 2 weeks for the rest of your life. It is important to discuss the benefits and limitations of ERT with a physician knowledgeable about Pompe disease and ERT.

People with Pompe disease often have problems with eating and swallowing. In late onset Pompe disease (LOPD), facial and oral (mouth) weakness gets worse which causes problems with chewing and swallowing. Swallowing problems and reflux (food or liquids coming back up the digestive tract) lead to an increased risk for aspiration (inhaling liquid or food into the lungs) which can lead to pneumonia. If someone with Pompe disease has severe swallowing or reflux problems, he/she can have a procedure to place a nasogastric (NG) or nasoduodenal tube (which goes through the nose into the stomach) or a gastro-jejunal tube (GJ tube, which goes through a hole in the belly into the stomach). Some people think that eating a high protein, low carbohydrate diet may help people with Pompe disease to reduce the buildup of glycogen, but studies have not shown a clear benefit yet. A registered dietitian may be able to help with meal planning to make sure individuals with Pompe disease get enough nutrients.

People with Pompe disease often have problems with eating and swallowing. Infants with Infantile onset Pompe disease (IOPD) have facial muscle weakness (hypotonia) and a big tongue, which causes problems with sucking. Swallowing problems can be caused by weakness as well and can lead to an increased risk for aspiration (inhaling liquid or food into the lungs) which can lead to pneumonia. If a baby is having severe issues with sucking and swallowing or with aspiration, a nasoduodenal tube (which goes through the nose into the stomach) or a gastro-jejunal tube (GJ tube, which goes through a hole in the belly into the stomach) can be used to feed the baby. Sometimes infants with IOPD who start enzyme replacement therapy (ERT) can start eating by mouth again once their muscles get stronger.

Pompe disease is caused by a missing enzyme in the lysosomes, which are like the recycling center of the cell. Missing this enzyme leads to build up of glycogen in muscle cells which damages the muscle cells. Muscle cell damage leads to weakness of the muscles needed to move the body (skeletal muscles), pump the heart (cardiac muscles), and move the lungs for breathing (respiratory muscles). The weakness gets worse over time.

In infantile onset Pompe disease (IOPD), the symptoms can start in the newborn period or even before a baby is born. The heart gets bigger than it is supposed to be and has more trouble pumping blood, called cardiomyopathy.

In late onset Pompe disease (LOPD), the heart is usually not involved, but the muscles the body uses to help the lungs move air in and out of the body (the diaphragm) becomes weak. Patients have slowly progressing symptoms and may not recognize they are somewhat unsteady on their feet, have trouble getting out of a chair into a standing position, even holding a blowdryer to dry your hair. Often it’s a loved one or someone close to a patient that may recognize the symptoms. Muscles affected first are those proximal (closest to the body) and then weakness travels to distal muscles (further away from the body). Shoulders, upper arms, pelvic area, and thighs are often first affected. Limb girdle muscles involving the pelvic and thighs are most often affected.

The only currently available treatment for either IOPD or LOPD is enzyme replacement therapy, in which a man-made version of acid alpha-glucosidase is infused into the body through a vein every two weeks. Over time, this enzyme breaks down the glycogen which has built up. It helps the heart get smaller and work better in IOPD. It helps people with IOPD and LOPD get better muscle strength. However, enzyme replacement therapy must be given every 2 weeks for the rest of a person’s life. Other treatments are being studied in clinical trials as well.

Babies with Pompe disease are often diagnosed based upon the symptoms seen at birth, but later onset Pompe disease may be more difficult to diagnose and require the involvement of multiple doctors who specialize in areas such as neurology (the nervous system) and metabolics (how the body turns food into energy). The best person to help figure out if someone has Pompe disease is their main doctor, who can then order testing or make referrals to the appropriate specialists.

The most common lung problems in infantile onset Pompe disease (IOPD) involve the inability to breathe well because the diaphragm, a muscle that helps the lungs draw in air, doesn’t work as well as it should. This causes less air in the lungs, a weak cough, and problems with breathing during sleep (sleep apnea). Infants with Pompe disease are more likely to aspirate (breathe in liquid or food) which can lead to aspiration pneumonia, an infection of the lungs. It can sometimes be hard to tell if infants are developing breathing problems because we can’t test a baby’s lung function by asking him/her to breathe in and out. Instead, the doctor will ask about how the baby sleeps during the day and the ability to do things like walk or eat without breathing hard. When someone can’t breathe deeply, they also can’t cough very well and so they build up secretions (fluid) in the lungs that can get infected, leading to pneumonia. Problems with breathing during sleep can happen before daytime breathing problems because the diaphragm has to work harder to move the lungs when a person is lying down. A sleep study can be done to find out if a child has sleep apnea and breathing machines can be used to help them breathe (for example, a CPAP machine). Sometimes infants and children with IOPD need help with breathing through a ventilator (breathing tube). A tracheostomy, commonly referred to as a trach, may need to be performed. It is a surgery that places a hole into the neck and into the trachea (windpipe) so that the breathing tube can be directly connected to the lungs. If a trach is done, it can be removed later if the child gets stronger and can breathe without the ventilator. A respiratory therapist is someone specially trained to help people manage their breathing problems, for example, there may be exercises that can help to strengthen the breathing muscles.

The most common lung problems in late onset Pompe disease (LOPD) involve the inability to breathe well because the diaphragm doesn’t work as well as it should. This causes less air to enter the lungs, a weak cough, and problems with breathing during sleep (sleep apnea). People with LOPD are more likely to aspirate, or breathe in liquid or food, which can lead to aspiration pneumonia (lung infection). Adults should have regular pulmonary function testing (PFTs) to determine how well the lungs are working. It is difficult to perform PFTs on children because they don’t always understand the instructions. When someone can’t cough strongly enough, they build up secretions (fluid) in the lungs that can get infected, leading to pneumonia. Problems with breathing during sleep can happen before daytime breathing problems because the diaphragm has to work harder to move the lungs when a person is lying down. A sleep study can be done to find out if someone has sleep apnea, and breathing machines can be used to help them breathe (for example, a CPAP machine). If a person develops respiratory failure and cannot breathe by himself/herself, he/she may need to be ventilated. A tracheostomy, commonly referred to as a trach, may need to be performed. It is a surgery that puts a hole into the neck and into the trachea (windpipe) so that the breathing tube can be directly connected to the lungs. If a trach is done, it can be removed later if the person gets stronger and can breathe without the ventilator. A respiratory therapist is someone specially trained to help people manage their breathing problems, for example, there may be exercises that can help to strengthen the breathing muscles.

The most common cardiac issues in infantile onset Pompe disease (IOPD) include cardiomyopathy (heart disease), heart failure, and arrhythmias (irregular heartbeat). Cardiomyopathy happens because of the buildup of glycogen in the cells of the heart muscle which makes the heart get bigger than it is supposed to be (hypertrophy). The buildup of glycogen also leads to conduction problems that can be seen on an electrocardiogram (ECG or EKG). These conduction problems should be treated with medication or a specific procedure called ablation because they can lead to serious health problems or sudden death if left untreated. Individuals with Pompe disease should have regular checks of their heart and may need to avoid certain medications. They should be seen regularly by their main doctor as well as a cardiologist (heart specialist).

Most people with Pompe disease have muscle weakness that leads to them having problems getting around. The muscles affected include those in the legs and hips that allow people to walk, stand up straight, and keep their balance. Some of the ways people can manage their weakness and improve mobility include:

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.

If someone has a family member affected with Pompe disease, prenatal testing can be done to look for Pompe disease in a pregnancy. If the specific changes in the GAA gene are known in the family, two tests are available during pregnancy. The first is called chorionic villus sampling (CVS) which is usually done between 10 to 14 weeks of pregnancy. It involves inserting a needle through the mother’s belly or cervix while an ultrasound is being done. The needle takes a little bit of the placenta, which is made from the same cells as the baby. The placental cells can be grown in a laboratory and tested to see if the placenta/baby has the two changes found in the family to cause Pompe disease. The second test is called amniocentesis (amnio) and is usually done between 15 and 20 weeks of pregnancy. With this test, a needle is inserted into the mother’s belly while an ultrasound is being done and takes a little bit of the amniotic fluid from around the baby. There are cells in the fluid that have washed off the baby that can be grown in a laboratory. These cells are tested for the 2 GAA changes from the family. Both CVS and amnio are considered almost 100% accurate but carry a small risk of miscarriage between 1 in 200 to 1 in 500, or between 0.2% to 0.5%.

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.

Pompe disease not only affects people affected with it, but their loved ones, too. It is important for caregivers of those with Pompe disease to take care of themselves as well. Schools should have special accommodations available for kids with Pompe. Below is the link for a teacher’s guide to neuromuscular diseases in general (which includes Pompe disease). In-home nursing care may be available through health insurance plans. Genetic Alliance has resources available to help you advocate for yourself and your child.

There are several clinical trials ongoing for Pompe disease. Alglucosidase alfa (Lumizyme®), an enzyme replacement therapy, is currently the only clinically available treatment for Pompe disease (PD). There are multiple ongoing clinical research projects to better understand Pompe disease and other medications. There are clinical trials on the horizon for other possible treatments for Pompe disease such as combination therapy and gene therapy. All clinical trials must be registered on clinicaltrials.gov. If you are interested in enrolling in research, visit the site regularly as studies change enrollment status often.

Antidote also offers a handy tool to find clinical trials.

Pompe disease causes weakness in the muscles used for moving the body, breathing, and swallowing. Sometimes the muscles of the heart are also affected. In newborns, the muscle weakness can be mistaken for other diseases that cause muscle weakness, but these other conditions usually do not cause a larger than normal heart with an enlarged left ventricle (one of the four chambers of the heart). Babies with infantile onset Pompe disease usually have a tell-tale sign on the electrocardiogram (EKG or ECG, a reading of the heart’s electrical activity) of their heart called a shortened P-R interval. In babies with muscle weakness and a large heart, Pompe disease should be one of the first things that the doctors test for.

Babies with Pompe disease are often diagnosed based upon the symptoms seen at birth, but later onset Pompe disease may be more difficult to diagnose because the symptoms are more general. The best person to help figure out if someone has Pompe disease is their main doctor, who can then order testing or make referrals to the appropriate specialists.

Pompe disease is variable in that symptoms can start anywhere from before birth to anytime in adulthood. A baby with infantile onsent Pompe disease (IOPD) has no acid maltase enzyme function and are born with muscle weakness and a larger than normal heart. When a person has late onset Pompe disease (LOPD), they have a little enzyme function. Symptoms of LOPD can start anywhere from 1 year of age to anytime in adulthood. People with LOPD usually do not develop a large heart (cardiomyopathy). Some changes in the gene (called mutations or variants) causing Pompe disease, GAA, are known to be severe and some are known to be milder. Individuals with Pompe disease will typically have two different mutations. If one of these mutations is milder (regardless of whether or not the other one is mild or severe), they usually have LOPD. At this time, we have not yet been able to determine when exactly symptoms will start or how fast they will progress.

Babies with Pompe disease are often diagnosed based upon the symptoms seen at birth, but later onset Pompe disease may be more difficult to diagnose and require the involvement of multiple doctors who specialize in areas such as neurology (the nervous system) and metabolics (how the body turns food into energy). The best person to help figure out if someone has Pompe disease is their main doctor, who can then order testing or make referrals to the appropriate specialists.

In the United States and other countries, there is an approved treatment for Pompe disease with a drug called alglucosidase alfa (Trade Name: Lumizyme). Lumizyme is an enzyme replacement therapy (ERT) which is a man-made enzyme that is infused into the vein of a person with Pompe disease every two weeks. The man-made enzyme can break down built up glycogen in the muscles. Lumizyme is better at clearing out glycogen storage in the heart muscles compared with the skeletal muscles (muscles which help the body move). It is important to start ERT as soon as possible when someone is diagnosed with Pompe disease, because muscle that is too damaged by glycogen may not be able to be helped. ERT therapy must be given every two weeks for the rest of the person’s life. It is very expensive, but health insurance usually most of the cost of the medicine. If you want to consider starting ERT, it would be best to go to a doctor experienced with prescribing ERTs for lysosomal storage diseases so that you can talk about the pros and cons of beginning ERT. There are other treatments for Pompe disease that are being studied in clinical trials (e.g., gene therapy, combination therapy).

There are many considerations when managing someone with Pompe disease. First, there are two forms of Pompe disease, an infantile or early onset and a late onset form. Babies with infantile Pompe disease (IOPD) are at risk for having severe heart problems (left ventricular hypertrophy, where one of the four chambers of the heart gets too big and cardiomyopathy, where the heart muscle is weak) as well as breathing problems and swallowing issues. Some children with IOPD need feeding tubes because they cannot swallow well and tracheostomies (trachs; an opening through the neck directly to the windpipe) to help them breathe through a tube. Because babies with IOPD are very weak, they do not move very much and can develop contractures (limited joint mobility), scoliosis (curved spine), and low bone density. Even though the heart reduces in size to normal with treatment with enzyme replacement therapy (ERT), kids with IOPD may still be at risk for heartbeat issues like supraventricular tachycardia (SVT).

In late onset Pompe disease (LOPD), the heart usually doesn’t get too large but people may still have heartbeat issues such as conduction blocks and should be seen regularly by a cardiologist (heart doctor). They can have breathing problems and swallowing issues and should be followed by a pulmonologist (breathing/lung doctor) with regular pulmonary function tests and a gastroenterologist (doctor for eating/digestion) with swallow studies. Both patients with IOPD and LOPD should have regular physical therapy. The only available treatment involves an infusion with a man-made enzyme through ERT every two weeks. Case managers at Sanofi Genzyme (www.genzyme.com) can help coordinate authorization through a person’s health insurance and location of infusions.

If you have Late onset Pompe disease (LOPD), there is a possibility that your full brothers and sisters also have Pompe disease. They should all be tested by either enzyme testing of the acid maltase enzyme or by testing the GAA gene for the 2 changes found in you (known mutation DNA testing). Both tests are blood tests. If your full brothers and sisters are not affected with Pompe, there is a 2 in 3 (66%) chance that they are carriers of one copy of the non-working gene and one copy of the working gene. As a carrier, they have no symptoms but can pass on the non-working gene to their children. The known mutation testing will find carriers, but the enzyme testing will not. If you want to find out who are carriers in the family, make sure to talk to your doctor about DNA known mutation testing.

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

Since Pompe disease affects multiple systems of the body, changes in routine and lifestyle may be required. For example, more time will be needed for medical visits and support may be needed for physical tasks. However, this doesn’t mean that someone living with Pompe disease cannot continue to do activities that he/she enjoys. Many activities can be modified to be less intensive. Individuals who work may need to discuss strategies with their employer to make their workplace easier to move around or to make hours more flexible. Schools may need to be involved to make similar changes for a student living with Pompe disease.

The more severe the muscle weakness is for someone with Pompe disease, the more the disease affects daily life. It can get harder to do physical activities such as walk, stand, or climb stairs when the muscles get weaker. An individual may need to get help or change their day-to-day routine to keep as much independence as possible. Although deciding to use a wheelchair can be difficult, it may help people to stay as active as they want to be.

Pompe disease is caused by a change (also called a mutation or a variant) in the GAA gene which causes the gene to not work correctly. The GAA gene carries the instructions for making the alpha-glucosidase enzyme, also called acid maltase, which is important for breaking down glycogen in the body. We normally have two working copies of GAA in our cells and we inherit one copy from our biological mother and the other from our biological father. In order to develop symptoms of Pompe disease, both copies of GAA are not working properly. This is also called autosomal recessive inheritance, which means that both parents of someone with Pompe disease are carriers of one working and one non-working copy of the GAA gene. Since each parent has one working copy, they don’t have symptoms of Pompe disease themselves. However, when they have children, they each have a 1 in 2 or 50% chance of passing on the non-working copy to their child. When both parents are carriers, there is a 1 in 4 or 25% chance of both of them passing on the non-working copy and having a child with Pompe disease. Even if a couple already has one child with Pompe disease, it is important to know that they can have another affected child because the chances are 1 in 4 for each pregnancy.

There are several support groups that support individuals with Pompe disease and raise money for research into better treatments. One organization is called the Acid Maltase Deficiency Association (AMDA). Another is the Muscular Dystrophy Association (MDA) which support people with many different muscle diseases, including Pompe disease. The Genetic Alliance is an umbrella organization which has information about support groups for many different organizations, including Pompe Disease. You can look up information about other groups at the Genetic Alliance website.

There are several ways to get tested for Pompe disease. Some states in the United States, including Missouri, New York, and Illinois (as of 2015), are performing newborn screening (NBS) for Pompe disease. This means that every baby in the state 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, the doctor will 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.

If possible, it is best to be followed by a doctor who has experience and expertise in Pompe disease. These doctors usually work in a clinic associated with the Muscular Dystrophy Association (MDA) or with a Lysosomal Storage Disease (LSD) clinic. MDA clinics can be found at [link url="www.mda.org” target=”_blank”>www.mda.org. If you have Pompe disease and have a case manager from Sanofi Genzyme, your case manager can give you the contact information for LSD or MDA clinics as well ([link url="www.genzyme.com” target=”_blank”>www.sanofi.com). Below is a small list of LSD clinics that follow patients with Pompe disease.

Pompe disease is a relatively common lysosomal storage disorder that affects around 1 in 40,000 individuals in the United States. The frequency of Pompe disease varies based on geographical region and ethnic background. There is an increased incidence of Pompe disease amongst Africa Americans affecting ~1:14,000 individuals. To learn more about how certain diseases can be more common in particular ethnic groups, see https://ghr.nlm.nih.gov/primer/inheritance/ethnicgroup.

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.

Pompe disease is a mendelian genetic disease, which means that it is primarily caused by one gene not working correctly (the GAA gene). It is possible that other genes, called modifiers, may affect the GAA gene’s function and make symptoms better or worse in certain people; this is still being researched. Because Pompe disease affects the way muscles work, regular exercise, a heart-healthy diet, and avoiding smoking are encouraged. However, there are no known lifestyle factors that make Pompe disease better or worse.

Intelligence is thought to be normal in infantile and late onset Pompe disease. Studies after the death of some patients with Pompe disease have shown buildup of glycogen in the brain and spinal cord, however, so it is possible that some minor damage may occur over time. This is becoming more evident now that people with Pompe disease are living longer with better treatments like enzyme replacement therapy. Children with IOPD often have speech that is hard to understand because of the weakness in their facial muscles and because they have more secretions as they are less able to swallow. Children with late onset Pompe disease may experience physical limitations as their muscle weakness worsens, but many have attended college and beyond. An evaluation by a developmental pediatrician is the best way to determine if a child has learning problems.

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).

Pompe disease is also called acid maltase deficiency, as well as glycogen storage disease type 2 because glycogen builds up in the body. There are several other types of glycogen storage diseases which are caused by changes in genes other than GAA. Some of these other glycogen storage diseases may have overlapping symptoms with Pompe disease, so it is important to have the right testing done to confirm if an individual truly has Pompe disease. The best person to help figure out if someone has Pompe disease is your primary care physician, who can order testing or make referrals to the appropriate specialists.

In addition to enzyme replacement therapy for Pompe disease, it is important to follow up regularly with several different medical specialists to manage different symptoms or possible symptoms of Pompe. First, it is recommended that everyone with Pompe disease be followed by a doctor who is knowledgeable about lysosomal storage diseases and/or Pompe disease. This may be a medical geneticist (genetics doctor), a neurologist (nerve doctor) in a Muscular Dystrophy Association clinic, or other doctor who has followed similar patients. Anyone with Pompe disease should follow regularly with a cardiologist (heart doctor) who may recommend an echocardiogram (ultrasound of the heart) and/or electrocardiogram (ECG; study of the heartbeat). A pulmonologist (lung/breathing doctor), gastroenterologist (GI; doctor for eating and swallowing issues), or an orthopedic surgeon (bone doctor) may also be needed depending on the symptoms. Regular physical, occupational, and speech therapy can be very helpful in helping to keep the muscles working longer.

There are several good support groups for Pompe disease. These support groups help explain Pompe disease features, inheritance, treatment, and research opportunities. They also raise money for research. One group is the Acid Maltase Deficiency Association and another is the United Pompe Foundation. The Muscular Dystrophy Association supports people with multiple diseases causing muscle weakness, including Pompe disease. There are several Pompe support groups on Facebook as well such as the International Pompe Association page and listservs such as GSDnet.

As far as the medical community knows now, all forms of Pompe disease are caused by changes in the GAA gene. There are no other genetic causes or things in the environment that cause Pompe disease.

Pompe disease has an early onset, severe form called infantile onset Pompe disease (IOPD) and a later onset form, called late onset Pompe disease (LOPD). A person has IOPD when they have no acid maltase (also known as acid alpha-glucosidase) enzyme function and are born with muscle weakness and a larger than normal heart.

When a person has LOPD, they have a little enzyme function. Symptoms of LOPD can start anywhere from 1 year of age to anytime in adulthood. People with LOPD usually do not develop a large heart (cardiomyopathy). Some changes in the gene (called mutations or variants) causing Pompe disease, GAA, are known to be severe and some are known to be milder. Individuals with Pompe disease will typically have two different mutations. If one of these mutations is milder (regardless of whether or not the other one is mild or severe), they usually have LOPD.

Babies with Pompe disease are often diagnosed based upon the symptoms seen at birth, but later onset Pompe disease may be more difficult to diagnose and require the involvement of multiple doctors who specialize in areas such as neurology (the nervous system) and metabolics (how the body turns food into energy). The best person to help figure out if someone has Pompe disease is their main doctor, who can then order testing or make referrals to the appropriate specialists.

Infantile onset Pompe disease (IOPD) can be mistaken for other forms of muscle diseases that are present in newborns such as Spinal Muscular Atrophy (SMA), Congenital Disorders of Glycosylation (CDG), Congenital Muscular Dystrophy, Prader-Willi syndrome, or mitochondrial disease. Newborns with these conditions all have very weak muscles and may have breathing problems. They usually do not (but can) have very large hearts like in IOPD. Babies with Pompe disease also have a tell-tale sign on the electrocardiogram (EKG or ECG, a reading of the heart’s electrical activity) of their heart called a shortened P-R interval.

Late onset Pompe disease (LOPD) is often misdiagnosed as other forms of muscular dystrophies (diseases where muscles get weaker over time), most commonly Limb Girdle Muscular Dystrophy (LGMD) because the symptoms are very similar. In both LOPD and LGMD, affected people start having muscle weakness in the upper arms and upper legs so the way they walk can look similar. People with LOPD can also have abnormally high liver function blood tests (markers called AST and ALT) which get mistaken as liver disease. The abnormal blood test is actually caused by the muscles breaking down. It is important to make the right diagnosis of Pompe disease, because unlike some of these other conditions, treatment is available to help make the muscles stronger or at least slow down the rate at which the muscles grow weaker. The best person to help figure out if someone has Pompe disease is their main doctor, who can then order testing or make referrals to the appropriate specialists.

While people with Pompe disease may be affected differently by the disease, it has been shown that a light training program with an aim to increase aerobic fitness, muscle strength, and core stability helps to improve fatigue and pain in adult patients with Pompe disease.