Pompe disease

The Pompe disease, also known as type II glycogen storage disease, is an autosomal recessive metabolic disorder that particularly affects muscle tissue and nerve cells. This disease leads to the pathological accumulation of glycogen in the lysosomes, caused by the low activity of the lysosomal acid α-glucosidase enzyme. As a result of Pompe disease, cells are unable to properly break down glycogen, which affects the functioning of various organs.

Lysosomes are specialized membrane-bound vesicles found in living cells that contain various enzymes. These enzymes are responsible for the breakdown of different molecules, including lipids, carbohydrates, proteins, and nucleic acids. Due to their acidic environment, lysosomes can effectively carry out degradation processes, as the enzymes within them work optimally in a low pH environment. Lysosomal storage diseases include Pompe disease, where glycogen accumulates in the cells because the enzyme responsible for its breakdown is either absent or not functioning properly.

The Causes and Mechanism of Pompe Disease

The underlying cause of Pompe disease is the deficiency of the lysosomal acid maltase enzyme. This enzyme’s role is to break down glycogen in the lysosomes, and if it is unavailable or present in reduced amounts, glycogen accumulates in the cells. This accumulation appears in various organs and tissues, with the heart muscle being particularly affected. Pompe disease is the only lysosomal storage disease that leads to glycogen accumulation, while other similar diseases involve the accumulation of different molecules.

Glycogen accumulation can be observed associated with the cell membrane of muscle fibers and within the cell itself. Since Pompe disease affects glycogen metabolism, it can be classified among glycogenoses, belonging to the category of type II glycogen storage diseases.

Forms of Pompe Disease

There are two main forms of Pompe disease: the classic infantile form and the late-onset variant. The classic form is characterized by a severe symptom complex, including reduced muscle functionality, cardiomyopathy, and enlargement of the liver and spleen. This form can lead to rapid deterioration and, unfortunately, often results in death by the end of the first year of life.

The late-onset form is rarer, with an incidence rate of about 1 in 40,000. Patients in this group may experience slowly progressive myopathy that can resemble limb-girdle muscular dystrophies. Respiratory failure may also appear in the early stages of the disease but can worsen as the disease progresses. In the late-onset form, patients may require mechanical ventilation, experience swallowing difficulties, and lose control over urination and defecation; however, cardiomyopathy is not characteristic of this form.

Treatment Options for Pompe Disease

Enzyme replacement therapy represents the only real therapeutic option for treating Pompe disease. The enzyme infusion therapy has already been approved by the U.S. Food and Drug Administration (FDA). This treatment can be life-saving, particularly in the case of the infantile form, as it improves cardiac and respiratory functions. In some cases, the therapy has led to significant improvements in motor functions, while in others, only minor changes in muscle strength were observed.

In the late-onset form, enzyme therapy can help prevent the progression of the disease. It is crucial to initiate enzyme treatment as early as possible, as delays increase the risk of the disease leading to irreversible consequences. Therefore, the treatment of Pompe disease is essential for improving the quality of life of patients and preventing complications.