Pompe disease is a rare genetic disease in which a complex sugar called glycogen builds up in the body's cells. This affects particularly the heart and skeletal muscles. Pompe disease occurs in about 1:40,000 births. There are two types of Pompe disease: type I is called infantile-onset Pompe disease (IOPD), and type 2 is referred to as late-onset Pompe disease (LOPD).
What Causes Pompe Disease?
People with Pompe disease lack an enzyme called acid alpha-1,4-glucosidase (GAA) that breaks down glycogen. Glycogen is a stored form of sugar, and an important source of energy in the muscles. There are many enzymes that can breakdown glycogen, but the GAA enzyme works specifically on the glycogen in the lysosomes, which are special compartments inside the cells of our bodies. For this reason, Pompe disease is also known as a glycogen storage disorder. When the body is not able to make enough GAA enzyme, glycogen builds up within the lysosomes, causing them to swell in size. These swollen lysosomes can interfere with normal muscle cell function. This leads to progressive muscle weakness, and in infants, enlargement and weakening of the heart. The level of GAA enzyme activity determines whether an individual has IOPD or LOPD.
Genes contain the instructions our cells use for making proteins, including enzymes, that are needed for our bodies to function properly. Pompe disease is caused by pathogenic variants in the GAA gene. Pathogenic variants are genetic changes in these instructions that lead to an enzyme that does not work properly.
Pompe disease is inherited in an autosomal recessive pattern. Everyone has two copies of each gene. We inherit one copy from our mother, and the other from our father. In conditions that are autosomal recessive, both copies of the gene must have variants that lead to a product that does not work properly. A person with Pompe disease has inherited a pathogenic variant in the GAA gene from each parent. This means the person has two non-functional copies of the gene and cannot make the acid-alpha glucosidase enzyme. The parents of someone with Pompe disease are referred to as “carriers,” and do not have Pompe disease, because one functioning copy of the gene is sufficient to maintain health.
Within each healthy muscle fiber, there are many myofibrils that are tightly packed and run parallel along its full length. They are represented by the large, light colored circles in the cross section on the left. The small, dark colored circles represent lysosomes which breakdown and process a sugar called glycogen.
In Pompe disease, the lysosomes are unable to breakdown glycogen properly and it builds up inside them. The lysosomes swell and sometimes rupture, (the dark colored circles representing the lysosomes are now large). This displaces the myofibrils and interferes with the normal function of the muscle.
What Are Signs & Symptoms of LOPD?
Late-onset symptoms appear as early as the first decade of childhood or as late as the sixth decade of adulthood. They may include:
Respiratory weakness (difficulty breathing)
What Are Signs & Symptoms of IOPD?
Early-onset symptoms appear in the first months of life. They may include:
Poor weight gain
How Is Pompe Disease Diagnosed?
There are several ways that Pompe disease may be diagnosed. A blood test is used to measure the GAA enzyme activity, and also to do a genetic (DNA) analysis looking for pathogenic variants in the GAA gene. In Illinois, Pompe disease is on the newborn screen, which means that all babies born in the state are tested in their first days of life for many disorders and conditions, including Pompe disease, that could benefit from early treatment.
How Is Pompe Disease Treated?
Enzyme replacement therapy (ERT) is the most common type of treatment for Pompe disease. The patient receives an infusion of the GAA enzyme through a vein on a regular basis. This has shown to be very beneficial as ERT helps decrease the enlarged heart, improves heart and muscle function, and reduces the accumulation of glycogen in the cells.
Symptoms of Pompe disease are also treated with supportive therapies. These include respiratory therapy and physical therapy to strengthen the muscles used for breathing.
Physiotherapy is also used to improve general strength and physical ability. Occupational therapy can help patients perform daily tasks. Orthopedic devices, such as braces, may be used to provide support for some patients.
What Are the Long-term Effects of Pompe Disease?
Each case of Pompe disease is unique, but in general, the later in life it arises, the slower it progresses. Infantile-onset Pompe disease progresses quickly, and the symptoms are severe. If it is not treated most infants will not survive past 18 months. With late-onset Pompe disease, the muscle weakness gradually gets worse over time. This eventually leads to serious breathing problems, but often many years later.
Pompe Disease Treatment & Research at Lurie Children’s
In addition, Lurie Children’s is a site for clinical trials to study new treatments for Pompe disease. Questions or inquiries for any of the clinical research trials can be directed to Rachel Katz, Clinical Research Manager, at RKatz@luriechildrens.org.
If you’d like to request an appointment, please call the Division of Genetics, Genomics and Metabolism at 312.227.6120.
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