Pompe disease belongs to a group of rare genetic disorders of metabolism, known as “glycogen storage diseases.” Pompe may also be referred to as:
- Glycogen storage disease type II
- Acid maltase deficiency
- Acid alpha-glucosidase deficiency
- Glyogenosis, type II
- Lysosomal alpha-glucosidase deficiency
What is metabolism?
Metabolism is a process by which food is broken down and converted into energy and other products that are needed by the body. This is a series of complex step by step processes, and often the food we eat is changed into many different forms before the body’s cells are able to use it to make energy. Metabolism is controlled by enzymes, which are natural proteins (or chemicals) in the body that help speed up the process. When one or more chemicals aren’t present or working properly in the body, that individual is not able to break down food, which then affects the amount of energy available to the cells in the body. Inside each cell of our bodies, there are structures known as mitochondria, which could be called the cell’s “engines.” Metabolic diseases are caused by problems in the way certain fuel molecules are processed before they enter the mitochondria, or by the inability to get fuel molecules, into mitochondria, all of which resulting in the mitochondria being unable to produce energy (or ATP).
What is Pompe disease?
Glycogen is a type of carbohydrate (or fuel) that is used to make energy in the body that is stored in the cells of the body. In most people, this glycogen is able to be broken down and leave the cell normally, meaning there is no accumulation of glycogen in the cell. The part of the cell responsible for the break down of glycogen is known as the lysosome.
In Pompe disease, the glycogen is not able to be broken down, resulting in excess glycogen building up in the lysosomes of those cells. This occurs due to a loss of activity of specific enzyme, known as acid alpha-glucosidase (also called acid maltase or GAA) which is encoded on chromosome 17. GAA’s role is to help break down the glycogen in the cells and when there is a loss of the GAA enzyme, the break down of glycogen cannot occur. The glycogen is then allowed to build up in the lysosomes, causing them to expand and eventually leak out glycogen that has built up. This causes progressive damage to the muscles, resulting in muscle weakness and loss of muscle function. The heart and lungs are also severely affected.
The following diagrams show the difference between a healthy muscle cells and muscle cells affected with Pompe disease:
There are two forms of Pompe disease; Infantile-onset Pompe disease and Late-onset Pompe disease.
Infantile-onset Pompe disease occurs from or shortly after birth (up to about 6 months) and is often the most severe form. Unfortunately, the condition progresses rapidly and is fatal.
Late-onset Pompe disease occurs anywhere from young childhood to adulthood. Some specialists may also refer to a childhood onset as a Juvenile form or Juvenile onset Pompe disease. Its severity is quite variable, however, generally, the earlier the symptoms present, the more rapid progression. Often in these cases, the best predictor of outcome is the patient themselves. The late onset form of Pompe often presents between the ages of 20 and 40, however, it may also be seen outside of this age group.
The signs and symptoms of Pompe disease may include:
- Low blood sugar
- Enlarged liver (hepatomegaly)
- Enlarged heart (cardiomegaly) and blockages of some vessels leaving the heart
- Enlarged tongue
- Slow growth
- Muscle cramps
- Progressive muscle weakness (including the respiratory muscles), which increases the risk of pneumonia.
- Heart complications
- Impaired alertness
- Secondary conditions such as infection.
- Intracranial aneurysms (in late onset form)
It is also important to note that individuals, who are affected with Pompe disease, often don’t tolerate anesthesic.
Diagnosing Pompe disease:
Often the diagnosis pathway is long and a process of elimination. This is because of the rarity of the condition. Unfortunately, Pompe disease looks like a lot of other, more common muscular dystrophies and therefore, these other conditions need to be rules out first. The testing process you might undergo (or have already undergone) includes:
Initial, nonspecific tests used to support of the diagnosis of Pompe disease:
- Serum creatine kinase (CK). CK is an enzyme that is released from the cells in out body when they become damaged. In Pompe disease, the glycogen is damaging the cells and causing them to release CK in the blood. Therefore, the levels of CK can determine how much the cells are damaged by the concentrations of it in the blood. This happens normally in the body after exercise and injury; therefore, the levels are taken 3 times over a number of weeks. The types of results you might get from this test include: uniformly elevated concentrations in classic infantile-onset Pompe disease and in the juvenile form, or, normal levels in the adult-onset form. It is important to remember that, serum CK concentration is elevated in many other conditions and is therefore not diagnostic. It is used to point the doctors in the right direction.
- Urinary oligosaccharides (sugars in urine). Because the extra glucose can leak out of the cell, it too can be tested for in the urine. Elevation of a certain urinary glucose is often seen in Pompe disease but is also seen in other glycogen storage diseases.
Specific testing used to establish the diagnosis of Pompe disease:
- Acid alpha-glucosidase (GAA) enzyme activity. Measurement of GAA enzyme activity is most reliably performed using skin cells. It may take four to six weeks to obtain results, with the results possibly including:
- Complete deficiency (activity <1% of normal levels) of GAA enzyme activity is associated with classic infantile-onset Pompe disease.
- Partial deficiency (activity that is 2%-40% of normal levels) of GAA enzyme activity is associated with the juvenile and late-onset forms.
- The amount of acid alpha-glucosidase proteins in the blood can analyzed by performing to determine if there is in fact a deficiency in that individual. This testing can be of value when interpreting the results from the GAA enzyme activity testing, by evaluating the amount of protein present.
- Muscle biopsy. In contrast to the other glycogen storage disorders, Pompe disease is also a lysosomal storage disease. In Pompe disease, glycogen storage may be observed in the lysosomes of muscle cells, when some parts of an affected cell react with a specific dye. However, in a small number of individuals with late-onset Pompe disease with documented partial enzyme deficiency may not show these muscle-specific changes
- Genetic Testing: Once the health professional is confident that the condition is actually Pompe disease, genetic testing on the GAA gene (the gene responsible for causing Pompe disease) can be performed to see if there is a change in the gene. Types of testing that may be done include sequence analysis and deletion/duplication analysis, both of which are able to pick up very small changes in the gene. Genetic testing usually requires a blood test to obtain the DNA they need.
- Enzyme replacement therapy such as Myozyme® can reduce the progression of Pompe disease, with the long-term prognosis not yet known (because the . Myozyme® (alglucosidase alfa) can be used for infantile Pompe disease with current trials for the use of Myozyme® for later onset conditions currently being undertaken.
- If there is exists and management is focused on supportive care.
- Diet therapy may be helpful. A high-protein, low carbohydrate diet may be beneficial.
- Recombinant human acid alpha-glucosidase enzyme therapy has been shown to improve cardiac and skeletal muscle function.
- Without treatment, the infantile form often results death within 1 year of birth. However, with Enzyme replacement therapy (ERT), there is a hope that children will live a longer, healthier life. Because the treatment is so new, it is unknown at this stage what the prognosis is for a child undergoing Enzyme replacement therapy, however, studies have suggested that children who have had this testing do have significantly improved health.
- Later clinical onset usually corresponds with less severe symptoms and disease progression.
- The adult form has a much better prognosis however, complications such as rupture of an aneurysm or respiratory failure can occur. Therefore surveillance and monitoring of symptoms is required.
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