Pompe Disease

Pompe disease is a glycogen storage disease with an unpredictable course. The symptoms are characterized by progressive muscle weakness. In the meantime, successes have been observed in therapy through the artificial administration of the causative enzyme.

Pompe Disease

What is Pompe disease?

Storage diseases are a heterogeneous group of diseases in which various substances are deposited in organs or cells of the organism. The tissues or organs usually lose their function due to the deposits. The deposited substances can be of different types. Depending on the substance, a distinction is made between glycogenoses, mucopolysaccharidoses, lipidoses, sphingolipidoses, hemosideroses and amyloidoses. In glycogenosis, glycogen is stored around body tissues. See growtheology for Comprehensive Guide to Bovine Spongiform Encephalopathy (abbreviated as BSE).

In the case of the disease, the stored carbohydrates can no longer be broken down or can only be broken down incompletely or transformed into glucose. The cause is usually an enzyme defect in the enzymes involved in the conversion of glucose in the body. A glycogen storage disease is Pompe disease, also known as Pompe disease or acid maltase deficiency. The disease affects the lysosomal α-glucosidase or acid maltase on gene GAA.

In a healthy body, the enzyme breaks down the long-chain polysaccharides of the lysosomes into glucose. In humans, the enzyme is present in all tissues. Nevertheless, the metabolic disease is mainly noticeable in the muscles and is therefore also assigned to the myopathies. The rare disease is named after the Dutch pathologist Pompe, who first described the phenomenon in 1932. In 1954 GT Cori documented the disease as glycogen storage disease type II.


In the 1960s, HG Hers discovered the lack of lysosomal α-glucosidase as the causal link in Pompe disease. This deficiency arises on the basis of a primary causative gene defect affecting the enzyme α-1,4-glucosidase. Also known as acid maltase, this enzyme is either absent or has reduced activity. This means that the musculature does not break down the sugar storage form glycogen. Glycogen is therefore stored in the muscle cells of the lysosomes, where it destroys the muscle cells. The residual activity of the enzyme correlates with the severity of the disease.

The infantile type of Pompe disease has activities of less than one percent. The juvenile type has a residual activity of up to 10 percent and the adult type has a residual activity of up to 40 percent. The disease is subject to autosomal recessive inheritance. Boys are affected just as often as girls. The causative gene defect was localized to the region q25.2-q25.3 of chromosome 17 and is 28 kbp long.

The disease is genetically heterogeneous and has so far been associated with 150 different mutations. The patients are compound heterozygous. The infantile form is often characterized by two severe mutations. In this form, there is a high level of agreement between the genotype and the course of the disease. This is not the case with the adult form. The prevalence is given with values ​​between 1:40,000 and 1:150,000. About 200 people are diagnosed in Germany.

Symptoms, Ailments & Signs

The main symptoms of Pompe disease are cardiomegaly and heart failure. Neurological and muscular deficits are also present. The onset of Pompe disease is not limited to a specific age, but can affect all age groups. The infantile form occurs in infants and usually ends fatally in the first year of life. Most of the time, the death that occurs is death from heart failure, which is due to hypertrophic cardiomegaly.

The first symptoms appear in the infantile form after two months. Adolescents develop juvenile Pompe disease. In adults, medicine speaks of adult Pompe disease. These forms are symptomatic of progressive muscle weakness in the respiratory muscles and the skeletal muscles of the trunk. The upper arms can be affected as well as the pelvis and thighs. The course is unpredictable in the adult and juvenile form. Severe courses are characterized by a loss of breathing ability.

There is also often a loss of mobility. States of exhaustion set in. In some cases, substances build up in the arteries and can form an aneurysm, which if ruptured can be fatal. On average, the first symptoms become noticeable shortly before the age of 30 and correspond to difficulties with running or sports. The diagnosis is usually made in the mid-30s. Around ten years later, those affected are mostly dependent on a wheelchair.

Diagnosis & course of disease

The diagnosis of Pompe disease is usually confirmed by a muscle biopsy based on the medical history. Histologically, the massive glycogen deposits in the muscle can be demonstrated in the PAS stain. The diagnosis can just as well be anchored in an enzyme activity measurement of the acid maltase, as can be detected in the leukocytes with the dried blood test. Molecular genetic tests can also be used to confirm the diagnosis. CK, CKMB, LDH, GOT and GPT are increased in the blood. Elevated Glc4 is usually present in the urine.

Numerous differential diagnoses must be ruled out. In the case of the infantile form, the suspected diagnosis can often be confirmed by the rapid progression, which is associated with increasing respiratory problems and delayed motor development, because of the pronounced symptoms. Cardiomegaly can be confirmed by X-ray findings. Theoretically, a prenatal diagnosis based on the amniotic fluid test or tissue removal is also conceivable.

The course of Pompe disease is generally more severe the earlier the disease breaks out. Nevertheless, Pompe disease is characterized by an individual and therefore actually unpredictable course of the disease. Mild forms are also observed.


Those affected by Pompe disease suffer from considerable limitations and complaints in everyday life. This primarily leads to breathing difficulties, which lead to a greatly reduced resilience and fatigue in the patient. Furthermore, the lack of oxygen can also lead to a loss of consciousness, in which the person concerned can possibly be injured by a fall.

The breathing difficulties also have a negative effect on the heart and other internal organs, so that irreversible consequential damage can occur to the organs. Life expectancy is significantly reduced and limited by Pompe disease. In the worst case, the person affected can die of cardiac death. Strenuous activities or sporting activities are still not possible for those affected by this disease.

The treatment of Pompe disease is usually based on the symptoms and aims to increase life expectancy. Various drugs are used, which usually do not lead to any particular complications. The symptoms can also be reduced with the help of physiotherapy. If there are psychological limitations, psychological treatment is still necessary.

When should you go to the doctor?

Anyone who suffers from Pompe disease is either already affected by the hereditary disease as a child or only complains about severe symptoms in the muscles as an adult. People with type II glycogenosis suffer from progressive muscle wasting. The respiratory muscles can also be affected. If the genetic defect is not discovered early in a routine examination, visits to the doctor become the order of the day as the symptoms increase.

However, it can take a long time to diagnose. First, there are many diseases that have a similar course. Second, genetic testing is not commonplace in medicine. Third, type II glycogen storage disease is also a metabolic disease. Many doctors are not familiar with the symptoms of Pompe disease. In addition, there is no uniform complaint for Pompe disease that occurs late. In children, the disease is much easier to diagnose.

Most adult patients go to the doctor with a variety of muscle complaints. The symptoms described can affect the extremities, but also the respiratory muscles or the heart. Organs such as the liver can also be affected. The decay is progressing rapidly. Therefore, visits to the doctor increase over time without the correct diagnosis being made. An odyssey through the practices is not uncommon in Pompe disease.

Treatment & Therapy

There is currently no cure for Pompe disease. A causal treatment of the symptoms is not available. Therefore, the patients are mainly treated symptomatically and supportively. Palliative forms of therapy are recommended. This therapy includes diet recommendations and breathing – as well as physiotherapy to strengthen the muscles. In the course of this, ventilation and artificial nutrition become necessary.

The timely decision for these measures is absolutely necessary to prolong life. In terms of nutrition, a protein-rich diet in combination with endurance training has proven itself. Since 2006, an artificial delivery of the recombinant protein made up of CHO cells and known as alglucosidase alfa or Myozyme has been possible. The medication is administered intravenously every 14 days. Pioneering successes were observed in infants after early administration of the drug, which could ensure survival.

There is conflicting experience with older children and there is no convincing evidence of the effectiveness of the adult form. The cost of medication can be up to 50,000 euros per year for an infant and up to 500,000 euros per year for an adult. Lifelong care is necessary. Skeletal muscle response to therapy is variable. In return, the heart muscle weakness improves. Because of the blood-brain barrier, the drug does not affect disease processes in the brain.

Therapeutic approaches such as gene therapy are in the animal experimental stage. Gene transfer has already been successful in mice. Treatment with pharmacological chaperones can increase the residual activity of acid maltase, but has not yet been used in practice. Supportive psychotherapeutic care to deal with the situation is recommended for affected families.

Outlook & Forecast

Pompe disease is an incurable hereditary disease that usually results in a shortened life expectancy. The exact prognosis depends on the specific form of the disease and the age of the person affected at the onset of the disease.

The prognosis is most unfavorable for the early form of Pompe disease, which usually leads to death within two years if left untreated. Those affected usually die of pneumonia or heart failure. Treatment of the disease with enzyme replacement therapy significantly improves the prognosis. The life expectancy of those affected increases significantly to an age of over ten years. Since this form of therapy is new, there are no long-term prognoses.

The juvenile form of Pompe disease, if left untreated, usually results in death before the patient reaches adulthood. The adult form of Pompe disease has the best prognosis. In any case, life expectancy increases significantly with treatment. However, those affected usually develop some limitations such as cognitive difficulties and hearing loss up to deafness. New treatment options such as gene therapies for Pompe disease are currently being developed and tested, which should lead to a much better prognosis.


So far, Pompe disease can only be prevented by genetic counseling during the family planning phase. For the parents of an affected child, the risk of recurrence is 25 percent. After a positive prenatal diagnosis, expectant parents are also given the option of an abortion.


As a rule, those affected by Pompe disease only have very few and only very limited measures and options for aftercare, so ideally they should see a doctor at an early stage to prevent the occurrence of other symptoms and complications. It cannot heal on its own, so a doctor should be consulted at the first signs and symptoms of the disease.

The recovery process is primarily based on exercises from physiotherapy or physiotherapy. Many of the exercises can also be repeated at home, which significantly promotes the treatment. The help and care of one’s own family is also very important, which can also prevent depression and other mental disorders.

In the case of an existing desire to have children, those affected should seek genetic testing and counseling to prevent the disease from reoccurring. Regular checks and examinations by a doctor are also necessary in the course of life. The disease itself usually does not reduce the life expectancy of the patient. Further aftercare measures are usually not available to the person concerned.

You can do that yourself

For those affected, Pompe disease is a very stressful diagnosis, especially if the disease only manifests later in life. The disease can take a very individual course, which is why the patients want to do as much as possible to ensure a mild course of the disease.

The main thing is to prevent additional diseases. For example, patients should ensure that they are well supplied with oxygen so that they do not fall due to dizziness or have an accident. In addition, a lack of oxygen would damage the heart – and possibly other organs as well. Infectious diseases such as the flu or common cold should also be avoided if possible, because they also impair breathing and weaken the body and its immune system to a great extent. Patients with Pompe disease are therefore well advised to pay special attention to their immune system. You should ensure a fresh, high-protein diet within the framework of the diet recommendations of your specialist doctor.

Regular exercise is also important to maintain muscle strength, especially in the legs. Endurance training in particular has proven itself in the treatment of Pompe disease. The treating physiotherapists provide the necessary assistance. Psychological support is helpful for many patients and their relatives. You will also receive support and information from Pompe Deutschland eV (www.morbus-pompe.de).