Once you are diagnosed with Pompe disease, you will need ERT for the rest of your life. This is the only way to keep glycogen from building up in the body. Keep reading to learn more about Pompe disease, how ERT works, and the side effects and adverse effects associated with ERT.
What Is Pompe Disease?
Pompe disease is a rare genetic disease that causes an abnormal buildup of glycogen, a sugar molecule, inside the body’s cells. That buildup will impair organ and tissue function. Pompe disease often affects the heart, the respiratory system, and skeletal muscles. It can lead to muscle weakness and breathing problems.
Pompe disease affects one in 40,000 people in the United States. It is an inherited condition caused by gene mutations in the gene that makes an enzyme called acid alpha-glucosidase (GAA).
This condition belongs to a group of disorders called lysosomal storage disorders. These disorders are inherited metabolic conditions where there is a toxic buildup of materials in the body’s cells due to enzyme deficiency.
Pompe disease is inherited in an autosomal recessive genetic pattern, which means you must inherit two flawed genes, one from each parent, to develop a condition. People who have only one mutated gene will not have symptoms of Pompe disease.
Symptoms of Pompe disease will be different depending on when they start and how much trouble they cause.
For babies under age 1, symptoms may include:
Feeding issues and not gaining weight Poor head and neck control, and late rolling over and sitting up Breathing problems, including lung infections A thickened and enlarged heart or heart defects Enlarged liver Enlarged tongue
Older children and adults who develop late-onset Pompe disease will have gradual symptoms that usually don’t involve the heart.
Symptoms of late-onset Pompe disease might include:
Weakness in the truck, legs, or arms Lung infections Shortness of breath and breathing troubles during sleep Spine curvature Enlarged liver Enlarged tongue, which can affect chewing and swallowing Stiff joints
There is no cure for Pompe disease, but symptoms can be managed to improve a person’s life expectancy. ERT is considered a first-line (initial) therapy that is generally started as soon as a diagnosis is confirmed.
Other treatments include support therapy—physical, occupational, and speech therapies—to enhance the quality of life, and improve muscle strength and food intake. Dietary changes can be helpful to ease difficulties if swallowing muscles are affected.
Muscles involved in breathing can be affected in late-onset Pompe disease. Early on, breathing difficulties appear during sleep, but as the disease advances, symptoms of hypoventilation will occur during the day.
Pompe disease can also cause impairment of cough muscles and airway clearance—both of which can lead to recurrent respiratory infections.
Mild symptoms of hypoventilation include tiredness, daytime sleepiness, shortness of breath, slow or shallow breathing, and depression. As the condition worsens and carbon dioxide levels go up, a person might experience bluish color of lips, fingers, or toes, headaches, confusion, and/or seizures.
According to a 2017 report in The Brazilian Journal of Pulmonology, respiratory discomfort affects 75% of people with Pompe disease, and respiratory failure is a major cause in this group.
Breathing problems in Pompe disease are managed with mechanical ventilation (assisted ventilation) to supplement or replace spontaneous breathing.
How ERT Works
ERT is used to treat genetic diseases, including Pompe disease, where there is an insufficient amount of an enzyme or the enzyme produced is not working as it should. It involves a functional enzyme produced in a laboratory using genetically modified cells. The cells are then collected, and the enzyme is purified before being used as a treatment.
ERT is also used to treat Fabry disease and Gaucher disease. Like Pompe disease, these two conditions are lysosomal storage disorders.
With ERT, alpha-glucosidase is infused directly into the bloodstream, where the body responds to it and breaks down glycogen to prevent a toxic buildup in the cells. With glycogen effectively managed, symptoms of Pompe disease are alleviated and disease progression slows down.
Once a person has been diagnosed with Pompe disease and starts ERT, they will need to keep treating with ERT for the rest of their life. If ERT is stopped, glycogen will once again build up in the body’s cells. Once started, ERT is rarely stopped even if a person experiences negative side effects.
ERT is linked to improved strength and energy levels, as well as higher survival rates. Unfortunately, ERT cannot resolve neurological symptoms and effects of Pompe disease.
Lumizyme (alglucosidase alfa) is the only ERT option available in the United States for treating Pompe disease. It is only available as an intravenous (IV) infusion and must be administered in a healthcare setting.
There is no generic for Lumizyme available, and it is an expensive drug even with insurance. Fortunately, the drug’s manufacturer offers a co-pay assistance program.
Side Effects and Adverse Reactions
Like all medicines, ERT comes with side effects. The most common side effects are due to the intravenous delivery of the drug. This might include needle site reactions, such as swelling or irritation.
The inflow of ERT fluid into the body can lead to electrolyte imbalance problems, which may include symptoms of nausea, lethargy, and fluid retention, or more serious effects, such as coma, seizures, or heart attack.
It is also possible to have an allergic reaction to the enzyme. The immune system may treat the drug as a foreign substance and attack it, leading to a severe allergic response such as anaphylaxis.
Additional side effects of ERT might include:
Muscle pain or tremorsFatigueNausea and vomitingRash, redness of the skin, or hivesFever, flushing, or feeling hotHeadacheCoughExcessive sweatingLess oxygen in the bloodFast heart rate or rapid breathingDizzinessChest discomfortHigh blood pressurePale skinBlue or purplish skin
With Pompe disease, doctors might prescribe higher doses of ERT to treat the condition, which means a higher risk for side effects.
Additional Treatments
While ERT is the only approved treatment for Pompe disease, research has looked at making the therapy more effective and reducing the side effects of therapy.
For example, researchers have looked at medicines like methotrexate which reduce the activity of the immune system. One study reported in 2013 in the Journal of Pediatrics founds that adding therapies like methotrexate could eliminate immune symptom responses against ERT.
Researchers have looked at the use of pharmacologic chaperones—molecules that help enzymes keep their shapes. According to a 2014 report in the journal Molecular Therapy, chaperones can ensure that an infused enzyme does not break down too early.
Chaperones also encourage the development of functional enzymes by assisting the body to fold enzymes correctly, which will reduce side effects.
A Word From Verywell
Because Pompe disease is a genetic disease, it cannot be prevented. And the outlook is dependent upon what organs might be affected. Fortunately, treatment with ERT can be helpful to people living the condition and allow them to live normal, productive lives.
The research on ERT and gene therapy for treating Pompe disease continues to grow and appears promising, which may lead to future improvements in outlook and quality of life for people living with the condition.
