A total of 45 different lysosomal storage diseases, which are a heterogeneous group of inherited metabolic diseases, are known. People who suffer from one of these diseases have a genetic defect. All storage diseases have one thing in common: a certain enzyme is not available or only partially functional.
What is a lysosomal storage disease?
According to Ablogtophone, these congenital storage disorders are rare, affecting fewer than five in 10,000 people. The various diseases progress very differently, and the symptoms can vary greatly.
The best-known forms of lysosomal storage disease are Fabry disease, Gaucher disease, Pompe disease, and mucopolysaccharidosis (MPS). They are often referred to as the “orphans of medicine” because the path to a specific diagnosis and appropriate therapy can be very long. Sometimes years can pass before those affected find out what is happening to them.
Lysosomal storage diseases are characterized by certain forms of hereditary metabolic diseases. The patients lack an important enzyme that ensures that the metabolic balance runs smoothly. In the less pronounced form, this enzyme is at least not present in sufficient quantities.
The task of enzymes is to dispose of pollutants and waste materials that accumulate in the human organism through metabolism via the lysosomes, or to process them again in such a way that there are no symptoms.
If there is an enzyme deficiency, this smoothly functioning disposal cycle is no longer guaranteed. The harmful substances settle in the cells and disrupt the metabolic cycle. In the initial phase, the disturbances do not have a noticeable effect, there are only a few restrictions. However, if this metabolic disease remains untreated as a result of an enzyme deficiency, the symptoms multiply, as the cells become greatly enlarged.
Symptoms, Ailments & Signs
In the worst case, they go under. The consequences are damage to the bones, nervous system, spleen, kidneys, muscles or heart. Morbus Fabry causes fat storage (globotriaosylceramide, Gb3) in the cells due to the reduced or absent enzyme activity. These unwanted deposits can lead to severe pain in the toes or fingers, stroke and kidney damage.
Diagnosis & course of disease
This clinical picture affects different systems at the same time: blood vessels, kidneys, heart and nervous system. Autosomal recessive Gaucher disease causes a mutation of the enzyme “beta-glucocerebrosidase” and leads to an accumulation of substrate inside the cells, especially in the macrophages (scavenger cells) belonging to the reticulo-endothelial system. The blood picture changes, the liver and spleen are enlarged and the bones hurt.
The disease is progressive and mostly ethnic in origin, since most cases occur in people of Jewish descent. Pompe disease is also known as “acid maltase deficiency”. The clinical picture belongs to the group of glycogenesis type II. The affected persons lack the enzyme “alpha-1,4-glucosidase” (acid maltase) or it is not available in sufficient quantities. Due to the disturbed breakdown of glycogen in the muscles, patients suffer from destruction of the muscle cells in the form of sugar storage.
Mucopolysaccharidosis type I (MPS), also known as Hunter’s disease, has various clinical causes. Hurler’s disease is the most severe form and Scheie’s disease is at the end of the clinical pathogenesis. There are transitions of different characteristics between these two courses. The salient feature is the disturbed breakdown of carbohydrates, which accumulate in the lysosomes of the cells.
Hunter disease patients may suffer from short stature, enlarged spleen and liver, coarse facial features, thickened skin, enlarged tongue, and breathing problems. In addition, the skeleton is often altered in the area of the pelvis, spine, hand bones and skull. Umbilical and [[hernias] are possible.
In most cases, this disease does not cause symptoms or complications until very late. For this reason, it is diagnosed late, so that early treatment is not possible in most cases. Without treatment, various symptoms and damage to the internal organs occur as the disease progresses.
The kidneys, liver and spleen are particularly affected. The heart can also be affected by this disease, so that in the worst case it can lead to cardiac death. Furthermore, damage to the kidneys occurs and those affected often suffer from pain in their toes or fingers. Paralysis can also occur if the brain has been damaged by this disease. The liver and spleen can be enlarged and also cause severe pain.
It is not uncommon for the affected person’s bones to be brittle and also painful. The treatment of this disease proves to be difficult. In many cases, the life expectancy of those affected is significantly reduced. When treated with drugs, there are usually no special complications. However, a positive course of the disease cannot be guaranteed in every case.
When should you go to the doctor?
Hair loss, joint problems and organ disorders are possible signs of a lysosomal storage disease. A doctor’s visit is recommended if the symptoms keep coming back or appear suddenly without a cause being found. If the symptoms occur in connection with an already diagnosed enzyme defect or another serious illness, the responsible doctor must be consulted. An untreated storage disease can lead to dementia, infertility, neuropathies and other complications, some of which are life-threatening. Therefore, all conceivable signs of illness should be examined, even if there is no concrete suspicion.
Symptoms of lysosomal storage disease can occur in phases or develop insidiously, but always require investigation and treatment. Affected people are best spoken to directly with their general practitioner or an internist. The actual therapy usually takes place in a specialist clinic for internal diseases, with physiotherapy or psychotherapy depending on the symptoms. In particular, therapeutic measures are indicated due to the often negative course of the disease.
Treatment & Therapy
Depending on how early an adequate diagnosis is made, these hereditary diseases can be treated very well with enzyme replacement therapy, so that the people affected have significantly fewer symptoms and thus a better quality of life. This replacement therapy is used according to the clinical picture.
People suffering from Gaucher’s disease lack the “enzyme ß-glucocerebrosidase”, which is biotechnologically produced and infused into the patient’s organism. Lysosomes act efficiently and are able to absorb substances from their immediate environment. For this reason, the artificially used enzymes are modified in such a way that they can be supplied to the lysosomes in an ideal way.
The macrophages (scavenger cells) break down the glucocerebrosides that have accumulated in the cells. This therapy can be compared to insulin therapy for diabetes mellitus, with the difference that it is not a missing hormone that is supplied, but an enzyme that is not present. The body regularly breaks down all substances, including the artificial enzyme supplied.
Due to this regular breakdown of substance, the patients have to undergo this infusion therapy regularly until the end of their lives. The enzyme replacement therapy does not act symptomatically, but directly combats the cause of the hereditary disease. Doctors describe this therapy as causal. The therapy principles apply to all four of the aforementioned common storage diseases.
Pompe patients are also treated with infusion therapy. In this condition, the nonexistent enzyme “acid alpha glucosidase” is supplied and helps break down glycogen that has accumulated in the lysosomes of the muscles. In patients with the disease type “mucopolysaccharidosis type I” the lysosomal enzyme “alpha-iduronidase” is not present or is not present in sufficient quantities. It is one of the rarest storage diseases in which sugar molecules accumulate in the organs and tissues.
In the normal course, the enzyme breaks down mucopolysaccharides. The sugar molecules have long chains and are involved in building supporting and connective tissue, such as bones, skin, synovial fluid and cartilage. If the normal course of degradation is disturbed due to the missing enzyme, pathological glycosaminoglycans (GAG) accumulate in the individual cells. Future therapy options are aimed at taking pills.
Outlook & Forecast
The prognosis of storage disease is unfavorable. A genetic disposition was identified as the cause of the health disorder. Legal requirements prohibit physicians and scientists from altering human genetics. For this reason, the disease persists for life and has no prospect of recovery.
The attending physician concentrates on the treatment of the resulting symptoms. If left untreated, various complaints will increase over time. The bone system is damaged and problems of the organs appear. In the worst case, there are functional difficulties in the internal organs and ultimately a failure of organ activity. This threatens the victim with premature death.
The challenge of the disease lies in the diagnosis. In a large number of patients, significant and strongly perceptible symptoms only appear later in life. As a result, the genetic disorder goes unnoticed for a long time and early treatment of the disease is made more difficult. The later a diagnosis is made, the more unfavorable the further course. In an advanced stage of the disease, the internal organs or joints are already severely damaged. Surgical interventions are required and in the event of an unfavorable course of the disease, only a donor organ can save the life of the person concerned. Therefore, early treatment is essential for an improved prognosis.
Since it is a congenital genetic defect that prevents the expression of an enzyme, this disease cannot be treated preventively. However, the latest achievements in genetic engineering could provide an approach in this field.
With this disease, sufferers suffer from a number of different complications and ailments. As a rule, these all have a very negative effect on the quality of life of those affected, so that a very early diagnosis should be made. The sooner a doctor is consulted, the better the further course of this disease.
The severity of this disease can be very different, so that a general prediction is often not possible. Those affected suffer severe damage to their internal organs. The kidneys and heart are primarily affected, so that the child can die in the first few days if the symptoms are not corrected in time. Fat is also deposited in different parts of the body.
The fingers and toes are particularly affected, which can lead to significantly reduced aesthetics for the affected person. As a rule, damage to the kidneys and the brain occurs in the further course, so that the person concerned dies as a result of this damage. Parents and relatives often suffer from depression or other mental disorders as a result of the illness.
You can do that yourself
Lysosomal storage diseases very often require intensive medical care. There are often not enough self-help options. The parents of affected children often experience severe stress in the home environment because their child requires constant care and attention.
The symptoms of the individual storage diseases are different. There are both light and very heavy forms. An example is Gaucher disease. Parental help is often limited to feeding the severely disabled child. In milder cases, life expectancy can be almost normal. Nevertheless, constant medical supervision is necessary to avert possible complications. Regular physical activity is one of the accompanying therapies that can also be carried out at home. Furthermore, a careful cancer screening test must be arranged. This requires parents to constantly visit the doctor with their child. The same applies to other lysosomal storage diseases.
In addition to physical disabilities, some illnesses can also lead to mental limitations that require special support. In milder forms of certain diseases, such as Hunter’s disease, only skeletal changes and facial dysmorphism initially occur. Here, however, the affected patient is often able to lead an independent life. However, constant medical examinations are also required here in order to rule out possible complications such as cardiac insufficiency or respiratory diseases. The patient can work through the psychological stress caused by the physical deformities through psychological counseling.