World Pompe Disease Day

What is Pompe disease?

Pompe disease is a multisystem, genetic, hereditary disease caused by mutation of the 'GAA' gene, which encodes information about the production and function of the GAA ('acid alpha-glucosidase') protein. What does this mean in practice? Glycogen, a complex sugar that is stored in the liver, is the initial form of fuel for muscles. During biochemical processes, it is broken down into the easily digestible simple sugar glucose. Deficiency or impairment of the GAA protein, in turn, impedes the conversion of glycogen into glucose.

In Pompe disease, skeletal muscles, smooth muscles, heart, as well as other tissues accumulate glycogen and, as a result of glycogen deposition, become damaged, which translates into impaired muscle structure and function. This causes patients to have problems with movement and respiratory function.

Symptoms of Pompe disease

In the classic pediatric form, the first symptoms of Pompe disease appear by the age of three months. Characteristic at that time is cardiac dysfunction due to cardiac hypertrophy. Infants affected by the condition suffer from general weakness of skeletal muscles. Since the development of all systems is at an early stage, the life expectancy of patients in this age group, if no treatment is implemented, is about two years.

Weakening of muscle strength is the first and main symptom of Pompe disease. Apart from the infantile form, cardiac problems (cardiac hypertrophy) are rare, due to the more developed body. Patients struggle with difficulty in movement and decreased respiratory function (to varying degrees).

The ways in which Pompe disease is clinically divided vary among authors of scientific publications. Some use the division into 'classic infantile', 'childhood' and 'adult' forms, while others categorize the condition by 'early' and 'late symptoms'.

Treatment of Pompe disease

If we talk about the treatment of Pompe disease, it should be divided into three categories:

• general treatment,
• Enzymatic Replacement Therapy,
• supportive therapies.

General treatment

The overall treatment process for Pompe disease sufferers is a joint effort of the entire interdisciplinary team, which includes specialists including pediatricians, neurologists, orthopedists, nutritionists, physiotherapists, cardiologists, internists, among others. The degree of involvement of each of them depends on the individual needs of the patient, as the entire treatment plan is based on them. In the case of genetic therapy, the care of a geneticist is also important.

Enzymatic Replacement Therapy

Enzyme Replacement Therapy involves intravenous administration of a replacement enzyme in the form of recombinant human acid alpha-glucosidase. Recombinant GAA does not fully cure Pompe disease, leaving residual symptoms, but nevertheless significantly prolongs life and improves comfort in many patients.

The main advantage of enzyme therapy is the stabilization of disease progression. Studies have shown that it is an effective form of treatment, despite the fact that in a negligible number of patients with poor prognosis, the administration of recombinant GAA sometimes causes deterioration.

Supportive therapies

Other forms of therapy, i.e. physiotherapy, occupational therapy, invasive or non-invasive respiratory support (mechanical ventilation), help from a speech therapist or orthodontist are aimed at improving, quality of life. They are selected according to the current individual needs of patients.

Because Pompe disease weakens muscles, replacement therapies focus on strengthening muscle strength, supporting breathing, learning to chew and swallow effectively, increasing physical fitness or providing orthopedic support for those with postural defects and impaired mobility.

Psychosocial problems of patients with Pompe disease

Psychosocial problems are one of the most important aspects to consider when planning the treatment and care of patients with Pompe disease. Rare diseases are chronic diseases. They cannot be cured. Therefore, not only the physical condition of the patient, but also the mental, emotional and social condition should be taken into account at every stage of therapeutic management.

What are psychosocial problems?

Wanting to talk about psychosocial problems, it is first necessary to define them precisely. These are all difficulties, ailments and hindrances in the sphere of psyche, emotions and proper functioning in society.

Psychosocial problems can affect any of us. Regardless of whether we are sick or healthy. However, people with chronic diseases, including rare diseases that are incurable, are particularly vulnerable to them. The reason for this, are so-called psychosocial risks and factors, which in patients with Pompe disease, include:

• Poor, prolonged and inadequate diagnosis
• Difficult access to pharmaceuticals to support treatment
• Inadequate access to rehabilitation and rehabilitation equipment, which have a significant impact on the comfort of life
• Poor organization of the health service, as well as related institutions, i.e. Medical Commissions, or Social Security
• Lack of facilities in public places for people with mobility disabilities
• Lack of support from family, friends
• Lack of acceptance of society, related to the patient's disability
• Public misunderstanding of the patient's condition and behavior
• Insufficient number of jobs and activities to activate chronically ill people
• Stress
• Isolation of chronically ill people from society
• Lack of adequate education of the public about rare diseases, including Pompe disease, and the problems resulting from it
• A sense of difference due to the fact that Pompe disease is a rare disease
• Fear caused by deteriorating health, especially increasing difficulty breathing.

It should be noted that despite major medical advances, Pompe patients still face diagnostic difficulties. According to statistics, a patient suffering from rare diseases hears a correct diagnosis after several years on average! During this time he has to struggle not only with physical suffering, but also learn to function with it in society, which often does not accept his deteriorating condition, accusing him of simulation and hypochondria.

Stress as one of the most important factors in worsening mental health in Pompe patients

Deteriorating physical health, the slow loss of psychomotor function and the lack of a correct diagnosis cause severe and chronic stress for people with Pompe disease. It should be specified that this is so-called distress, or stress, which negatively affects the human body, including its physical state. Thus, it causes the so-called vicious cycle. Among other things, uncontrollable muscle tension and panic and anxiety attacks occur, causing additional breathing problems, blood pressure rises, and tachycardia, or increased heart rate, occurs. It can also lead to isolation of the patient from society and even depression. It is worth noting that the lack of proper treatment and care for patients with Pompe disease, causes distress to persist for many years. During this time, there is usually already irreversible damage to the patient's body. Thus, the role of the doctor and nurse is to take a thorough history of the presence of stress factors in Pompe's patients and to closely monitor them for depression. This is because it should be remembered that undiagnosed and untreated depression, in patients with rare diseases, including Pompe's disease, can lead to their discontinuation of further diagnosis and treatment, and thus result in a faster progression of the disease and ultimately a quicker death.

Patients with rare diseases, including Pompe disease, should be helped to eliminate excessive stress by himself, his family, as well as his treatment team, including his family doctor, who is a general practitioner. His knowledge and experience in diagnosing rare diseases are very important. He is the main person who keeps track of the patient's condition and thus the responsibility for him.

Psychosocial problems faced by patients with Pompe disease

The psychological and emotional problems of patients with Pompe disease begin at the early diagnosis stage, when patients suffer, and are unable for many years to get answers as to why and how to relieve this suffering. Anxiety, frustration, discouragement from further testing (patients conclude that it won't show anything anyway), fear and social withdrawal ensue. Once a diagnosis is made, further problems arise. Hearing what the patient will have to live with next and what the consequences of the diagnosis will be, the patient goes through the five stages of acceptance of chronic disease, distinguished by American physician E. Kubler - Ross:

• 1. denial - the ill person does not accept the diagnosis, believes that a wrong diagnosis has been made (in the case of Pompe disease, once again), often demands a change of doctor, diagnostic center, repeat tests and additional diagnostics.
• 2. anger - the patient feels anger toward everyone and everything. He blames doctors, family, society and even God for the fact that the disease has affected him. He unloads his anger and frustration on those close to him, and is often aggressive, both verbally and physically.
• 3. bargaining - the sick person begins to bargain with God in the style of "if you allow a misdiagnosis, I will go on a pilgrimage," etc. In addition to God, the sick also expect doctors, nurses, physical therapists to make declarations and promises to heal him.
• 4 Depression - this is the stage when the patient realizes that the disease has affected him, it can not be cured, he will have to live with it, treat himself, overcome all the difficulties and struggle with its successive stages. As a result, fear, anxiety, depression appear. The patient begins to isolate himself from society, crying.
• 5 Reconciliation - there is an acceptance of the disease, seeking real help to address the problems that the patient will face.

Once a patient with Pompe disease has gone through all the stages of accepting the disease, he or she faces further problems. These include loss of work, due to the frequent L4 leaves the patient has taken to get diagnosed and now treated, architectural barriers when a person with Pompe begins to need mobility-assisting rehabilitation equipment, barriers that officials put up when the patient tries to get a disability rating, such as. repeated referrals for additional documents, extending the time until a date is set for the medical board, problems with obtaining rehabilitation or nursing benefits, as well as the lack of acceptance by society, the patient's slow exclusion by society from his current social life. Pompe patient may also experience financial problems, related to possible loss of work or reduction in employment, emerging costs of additional diagnostics, additional dietary supplements. Due to the occurrence of musculoskeletal, respiratory, circulatory problems, patients begin to be passive, even more so if they do not receive support from relatives and medical personnel.

Psychosocial problems of children with Pompe disease

When talking about the psychosocial problems of people with Pompe disease, it is also important to remember the youngest patients, namely children. A study conducted at Duke University Medical Center on a group of 21 juvenile patients with Pompe disease, aged 5 to 18 (IPD-early onset 17 patients, LOPD-late onset 4 patients) and one caregiver per child (19 mothers, 1 father, 1 grandmother) showed that mental and emotional functioning in children with Pompe did not deviate from the norm. Although the investigators acknowledge that parents of young patients reported that their children had moments of social withdrawal, as well as depressive symptoms. What's more, caregivers of patients under the age of 6 (the IPD form) confirmed problems with their preschoolers' emotional control. The present study showed that almost 50% of juvenile patients with Pompe disease have key problems in terms of inattention, and more than 1/3 were noted to have increased hyperactivity and impulsivity. It was also observed that young patients with IPD participated less frequently in sports and extracurricular activities than healthy children. Nevertheless, they felt comfortable in the company of their classmates whom they knew. Regarding school activities and learning, parents of children with IPD, reported that they had problems with concentration, reading, spelling and math tasks. Nevertheless, it should be noted that children with IPD attended the same school as healthy children and were also successful. Regarding young patients with the Pompe form of LOPD, the study found fewer emotional and social problems than with the IPD form.

Support and acceptance of society an important therapeutic element

Psychological and emotional support of Pompe patients is an extremely important part of the therapeutic process. It should appear as early as the patient's early diagnosis and suspicion of the possibility of the disease. Who should support people with Pompe disease? First and foremost, the family. This is regulated by Article 87 of the CRC, Journal of Laws 2020.1359, i.e. "Parents and children are obliged to respect and support each other." It is worth noting that this article does not refer only to financial support in the difficult financial situation of a family member, but also to the health situation and assistance in this direction. It is also clear that a young child cannot be burdened with caring for a disabled family member.

In addition to family, Pompe sufferers should also be supported by close friends, their family doctor, specialist physicians, physical therapists and rehabilitation specialists. It is important that the treatment team should also include a psychologist with experience in helping people with Pompe disease, or at least with experience in helping people with chronic diseases, and, if necessary, a psychiatrist. Both the patient himself and his family should also seek advice and help from support groups, associations and foundations, especially those that bring together people with the same disease entity.

One of the elements of psychological and emotional support for patients with Pompe disease is their acceptance by society. Unfortunately, despite advances in medicine and extensive educational activities spreading health promotion and knowledge of chronic and rare diseases, society still largely turns its back on people who have to deal with an incurable disease. This can be explained by fear of the unknown. Hence, the role of doctors and nurses is to spread awareness and knowledge among the public about rare diseases, and thus the problems of Pompe patients.

It should be borne in mind that the lack of support and acceptance of the pathological changes taking place in the body of a Pompe sufferer can cause him or her to become more depressed and resolutely reluctant to continue treatment, which can have tragic consequences. The onset of symptoms, the subsequent deterioration of the condition, and the lack of proper diagnosis and treatment cause Pompe patients to become nervous, frustrated, and stressed. This, in turn, leads to a weakened immune system, which loses its ability to defend itself against pathogens, thus being vulnerable to additional infections and chronic comorbidities. It should be remembered that Pompe patients have cardiovascular problems, among others, and stress puts additional strain on the heart, which can lead to more frequent arrhythmias and cardiomyopathies.

Improving quality of life in people with Pompe disease

During a study performed in 2018, in China, based on the WHO Abbreviated Quality of Life Assessment Scale, on the quality of life of 68 adults suffering from Pompe, it was concluded that employment had a very strong impact on improving the quality of life of people with the disease. Patients who were able to work showed greater efficiency in all aspects of life. In addition, it was noted that activating the patient and involving him in social life improved his quality of life.

In the UK, 27 patients with late-onset Pompe disease were interviewed about their quality of life. In them, they very often mentioned that they would like GPs to give them more support during the diagnostic stage. These patients also expressed the need to educate these medics more about their condition, as according to them, the diagnostic time from onset to correct diagnosis was too long. They also faced at least one additional misdiagnosis before it occurred. During this time, they experienced emotions such as fear, anxiety, loneliness, anger and denial.

In contrast, a study conducted on an international population of Pompe patients, i.e. 210 people from Austria, the United States, the Netherlands, Germany and the United Kingdom, showed that there were no significant differences between the perception of quality of life about patients in the above countries. Patients admitted that their quality of life was affected by their physical deterioration, but also by their social condition.

Source: press mat.