Juvenile Glycogenosis Type II: Causes, Symptoms & Treatment

Juvenile glycogenosis type II is a glycogen storage disease. It is also known as Pompe disease.

What is juvenile glycogenosis type II?

Juvenile glycogenosis type II is a rarely occurring metabolic disorder that is hereditary. Because it occurs primarily in the muscles, physicians also include it among the myopathies. Other names for juvenile glycogenosis type II are Pompe’s disease, Pomp’s disease, Pompe’s disease, generalized glycogenosis or malignant glycogenosis. The name Pompe’s disease goes back to the Dutch physician Johannes Cassanius Pompe (1901-1945). He described the disease for the first time in 1932. In 1963, H.G. Hers discovered that the absence of lysosomal alpha-glucosidase is responsible for juvenile glycogenosis type II. The adult form of Pompe disease was described by A.G. Engel in 1969. Juvenile glycogenosis type II occurs very rarely. In Germany, for example, there are only 100 to 200 people who suffer from this hereditary disease. In the entire world, there are said to be between 5,000 and 10,000 people.

Causes

Juvenile glycogenosis type II is caused by a genetic defect. As a result of this, the enzyme alpha-glucosidase, also known as acid maltase, is produced by the organism in insufficient amounts or not at all. Normally, the enzyme has the function of breaking down glycogen. Glycogen is a special form of sugar. It is stored in the muscles of the skeleton and the heart. Lysosomes are described as small cell organelles that function like a temporary storage facility. If there is an excess of glycogen within the lysosomes, the cells are affected, which has a negative effect on the entire musculature. Because glycogen accumulates in the lysosomes, this is referred to as lysosomal storage disease. The gene for the blueprint of alpha-glucosidase is present on chromosome 17. For an onset of juvenile glycogenosis type II, a defect of the alpha-glucosidase gene of both the mother and the father is required. Thus, Pompe disease is one of the autosomal recessive inherited diseases.

Symptoms, complaints, and signs

Pompe disease can be divided into three degrees of severity. In addition to juvenile (late-childhood) glycogenosis, these are infantile (early-childhood) and adult (adult) forms. Infantile glycogenosis is the term used when the disease begins shortly after birth. In this case, the affected babies suffer from severe muscle weakness, respiratory problems, lack of movement, dysphagia, enlarged heart, liver and tongue, and heart failure. It is not uncommon for the juvenile form to be fatal for the affected infants. Juvenile glycogenosis type II, on the other hand, does not manifest itself until early childhood. It is characterized by gait disturbances and increasing muscle weakness. In addition, the weakened respiratory muscles can result in respiratory infections and breathing difficulties. The heart is rarely affected in this form. In adult glycogenosis, symptoms such as muscle weakness do not appear until adulthood.

Diagnosis and course of the disease

Because juvenile glycogenosis type II is a very rare disease, it must be considered as a possibility by the treating physician in the first place. In principle, however, the diagnosis can be made relatively easily by a blood test. Here, the white blood cells are examined for a defect in the alpha-glucosidase enzyme and a high content of glycogen. Another diagnostic option is to take a tissue sample. This can also be checked for glycogen content as well as alpha-glucosidase activities. Among the abnormalities that can be detected microscopically is the enlargement of the lysosomes. Also possible is a skin sample from which connective tissue cells are cultured. The course of juvenile glycogenosis type II varies and cannot be predicted. Both mild and severe courses of the disease can occur. In a severe course, affected individuals are no longer able to move independently and often require artificial respiration. The earlier Pompe disease occurs, the less favorable the course of the disease. However, mental abilities are not affected by glycogenosis.

Complications

Glycogenosis type II usually results in a number of different complaints. Most patients suffer mainly from dysphagia and respiratory complaints. Furthermore, the muscles can also be severely weakened and heart failure occurs. In the worst case, this can lead to the death of the patient, especially if no early treatment is initiated. Similarly, severe gait disturbances and movement restrictions occur. The respiratory tract can also be infected by glycogenosis type II, so that life expectancy may be reduced. In many cases, the symptoms do not appear until adulthood, so early diagnosis is not possible. Glycogenosis type II can be treated relatively well with the help of medication. As a rule, no particular complications occur. Furthermore, acute emergencies can also be treated directly by an emergency physician. This is the case if severe headaches or dizziness occur. In this case, the affected person may also lose consciousness and possibly injure himself in a fall. Not infrequently, this also results in rashes on the skin.

When should one go to the doctor?

Breathing problems should always be examined by the affected person as soon as possible. If an undersupply of oxygen to the organism occurs over a longer period of time, life-threatening conditions can develop, which must be responded to in good time. In severe cases, rescue services must be alerted in the event of respiratory failure. If anxiety sets in or if family members notice interruptions in breathing during night sleep, a physician must be consulted. If there is difficulty swallowing, a refusal to eat, or weight loss, a doctor must be consulted. If the body is not supplied with sufficient fluids for several days due to the symptoms, a feeling of internal dryness develops. A visit to the doctor must be made immediately, since dehydration threatens the premature death of the affected person. If there is a reduced formation of the musculature, there is a lack of movement or an apathetic behavior, a doctor is needed. The symptoms described can occur in children as well as in adults. To avoid sudden death, consultation with a physician is required early at the first warning signs. Swelling of the chest, a feeling of tightness inside the body, or a diffuse sensation of illness should be presented to a physician. If gait unsteadiness, an enlarged tongue, or disturbances in heart rhythm occur, a doctor’s visit is also necessary.

Treatment and therapy

Treatment of juvenile glycogenosis type II has taken place in Germany since 2006 by enzyme replacement therapy (EET), which involves the use of myozymes. The therapy is performed in all patients in whom the diagnosis of Pompe disease is confirmed. As part of the treatment, the patient is administered the missing alpha-glucosidase enzyme at two-week intervals. The enzyme is administered by intravenous infusion. The enzyme is transported to the cells via the bloodstream. Once there, it couples to the lysosym receptors, allowing it to penetrate the interior of the lysome. In healthy people, metabolism proceeds similarly. The effectiveness of enzyme replacement therapy is difficult to assess. Thus, it depends on the initial situation. An early start of therapy is considered crucial for the success of the treatment. The infusion is administered on an outpatient basis, so hospitalization is not usually required. Sometimes the infusions can trigger side effects that occur about two hours after treatment. These include dizziness, skin rashes, cough, nausea or headaches. Allergic reactions are also in the range of possibility.

Outlook and prognosis

A cure of the disease is impossible with the current medical as well as legal possibilities. There is a causal genetic defect in the patient, which may not be changed for legal reasons. Therefore, the treatment of the physicians is directed toward alleviating the existing symptoms and, in particular, toward supplying the missing enzyme. Lifelong therapy is necessary to achieve stabilization of health. As soon as the treatment is discontinued, the health condition of the affected person deteriorates within a few days or weeks.The sooner a diagnosis is made and enzyme replacement therapy is initiated, the better the prospect of alleviating the symptoms that have occurred. A complete avoidance of symptoms is currently not achieved despite all efforts. A restriction of the quality of life as well as the well-being remains. In addition, secondary symptoms may occur. Since the missing enzyme is supplied to the organism via the bloodstream at intervals of 14 days, side effects or complications can occur at any time. The general risk of infection is additionally increased in patients due to the circumstances. Although there are various risks associated with the use of this form of therapy, it nevertheless represents the best treatment option according to current scientific possibilities. A worsening of the prognosis is present as soon as a patient has an allergic reaction immediately after treatment.

Prevention

Juvenile glycogenosis type II is one of the hereditary diseases. For this reason, no prevention is possible. Couples affected by Pompe disease who wish to have children are advised to seek genetic counseling.

Follow-up

Juvenile glycogenosis type II can be treated in follow-up only with the necessary medical instruction. Preventive measures do not exist for the hereditary disease, so the recommendation for affected couples who wish to have children is genetic counseling. The relatively rare disease requires close medical attention. To keep the risk for patients low, consultation with the physician should always take place before possible self-help measures. Those affected are extremely susceptible to respiratory infections, which is why prevention against corresponding illnesses plays an essential role. Especially in the cold winter months, patients must not come into contact with infected persons. In any case, it is advisable to refrain from smoking. Sometimes the patients suffer from muscular weakness. In this case, the doctor advises physiotherapy. Patients should perform the corresponding exercises regularly, which is also possible at home after an introduction by a trainer. Here, too, a precise consultation with the therapist and the doctor takes place beforehand, so as not to put too much strain on the body. The medically prescribed medication must be taken regularly and exactly as instructed. Through this cooperation, patients can perceive an improvement, even if the disease is not curable.

This is what you can do yourself

Juvenile glycogenosis type II is a comparatively rare disease that should always be treated and managed by a specialist. Therefore, any self-help measures must always be coordinated with the treating physician first, so as not to put patients at risk. In general, affected individuals suffer from a particular susceptibility to respiratory infections. Therefore, it makes sense for patients to pay increased attention to the prevention of such diseases. Particularly during the cold season, patients avoid contact with appropriately infected persons. They also generally refrain from smoking. Some patients suffer from muscle weakness, so physiotherapy is of great importance for their quality of life. Patients perform the exercises they have learned at home without the help of the trainer, but only if this is expressly permitted by the therapist. Various drugs are now available for drug therapy, so that patients receive relatively good treatment. A prerequisite for successful therapy is the cooperation of the patients, who always attend medical examination appointments with various specialists.