Gauchers Disease (Gaucher Syndrome): Causes, Symptoms & Treatment

Gaucher disease is one of the most common lipid storage disorders and is due to a genetic deficiency of the enzyme glucocerebrosidase. In a large number of cases, the disease can be treated with enzyme replacement therapy, which causes a regression of symptoms characteristic of Gaucher disease.

What is Gaucher disease?

Gaucher disease (Gaucher syndrome) is a genetic lipid metabolism disorder caused by a deficiency of the enzyme glucocerebrosidase. As a result of the degradation disorder caused by this, increased glucocerebroside is accumulated in the organism, especially in the reticulum cells (fibroblasts in the connective tissue), which leads to an enlargement of the affected organs. Gaucher’s disease is differentiated according to three forms, which differ in terms of symptoms and course. The visceral or non-neuronopathic form is characterized primarily by organic impairments such as enlargement of the liver and spleen (hepatosplenomegaly), anemia (anemia), bone and joint disorders, and coagulation disorders. In the presence of acute neuronopathic Gaucher disease, affected individuals also exhibit damage to the nervous system. This form of the disease has a severe and strongly progressive course and leads to death in the first years of life. The chronic neuronopathic form is characterized by a weakly progressive course with manifestation in later years of life.

Causes

Gaucher disease is an autosomal recessive inherited deficiency of the enzyme glucocerebrosidase due to mutational changes in the genetic material. Glucocerebrosidase is an enzyme that helps break down glucocerebroside, a fatty component produced during the breakdown of spent blood cells. The cells of people affected by Gaucher’s disease are not able to produce this enzyme in sufficient quantities or produce glucocerebrosidase in reduced quality. As a result, glucocerebroside accumulates in the macrophages (phagocytes). The macrophages accumulate with the undigested glucocerebroside mainly in the spleen, liver, as well as bone marrow, causing the organ enlargement typical of Gaucher disease, which limits the function of the affected organs.

Symptoms, complaints, and signs

Gaucher disease can occur in three different forms, each with different symptoms. The mildest form of the disease is type I, with a non-neuronopathic course. Type II characterizes the acute neuronopathic course, while type III of the disease represents the chronic neuronopathic course. In Gaucher disease type I, the first symptoms usually appear in adulthood. In contrast to the other forms of the disease, there are no neurological symptoms. However, the internal organs are affected. Especially the spleen enlarges and causes such complaints as enlarged abdomen, upper abdominal discomfort and constant feeling of fullness. At the same time, blood cells are broken down more rapidly and blood formation in the bone marrow is impeded. This results in increasing anemia, which is manifested by fatigue and exhaustion. The immune system is weakened by the lack of white blood cells. Blood clotting is also reduced because too few platelets are produced. In addition, there is deformation of the bones, increased bone fractures and frequent infections. Bone pain, chronic joint pain and circulatory problems are also among the possible symptoms in the non-neuronopathic course. In type II Gaucher syndrome, the disease begins in infants with severe symptoms due to nerve degeneration processes. Increasing brain damage results in difficulty swallowing and severe seizures. Death occurs within two years. In the chronic neuronopathic course, slow nerve degradation processes take place with progressive mental deterioration, movement disorders, behavioral abnormalities, and increasing seizures.

Diagnosis and course

Gaucher disease is diagnosed on the basis of symptoms characteristic of the disease, such as spleen and liver enlargement (hepatosplenomegaly), bone and joint pain, spontaneous fractures, decreasing muscle tone, anemia, fatigue, seizures, and ocular fundus changes (white spots).The diagnosis is confirmed by a blood test and an enzyme test, in which the enzyme activity in the leukocytes or fibroblasts is determined. If an increase in phosphatase and a reduced concentration of glucocerebrosidase are found in the blood and Gaucher cells can be detected in the bone marrow, the diagnosis is confirmed. With timely initiation of therapy, the visceral and chronic neuronopathic forms of Gaucher’s disease can be expected to slow the progressive course of the disease and alleviate symptoms in most cases. The acute neuronopathic form, on the other hand, has a highly progressive course, and those affected with this form of Gaucher disease often die at an early age.

Complications

First and foremost, Gaucher disease causes severe enlargement of the spleen. This can also result in pain, which can significantly reduce the patient’s quality of life. In most cases, patients also suffer from enlargement of the abdomen and pain in the abdomen. In addition to the pain, there is also a loss of appetite, which can further lead to malnutrition or nutrient deficiency. Anemia also promotes fatigue and tiredness in the patient. The quality of life is significantly reduced by Gaucher’s disease. Pain in the joints or seizures can also occur and make the daily life of the affected person more difficult. It is not uncommon for very young children in particular to die from the symptoms of this disease, which can lead to psychological discomfort or depression in the parents and relatives of the patients. Treatment of this disease can take place with the help of infusions and other medications. Complications usually do not occur in this process. However, it is not possible to completely limit Gaucher’s disease, so in most cases patients are dependent on lifelong therapy. Whether there is a reduction in life expectancy depends largely on the treatment and on the severity of this disease.

When should you see a doctor?

In the case of hereditary fat storage disease Gaucher’s disease, those affected must expect that this rare enzyme defect will be misdiagnosed several times. Currently, only about 2,000 patients are registered with it in Germany. Therefore, every visit to the doctor necessitated by this genetic defect is initially a problematic one. The fact that the symptoms differ from person to person is already difficult. People affected by Gaucher disease often develop the disease as children. Some sufferers have hardly any symptoms at all. Consequently, they do not visit a doctor. If the enzyme defect causes precarious symptoms, a specialist should be consulted. Enough tests and symptom lists can be found on the Internet to make a corresponding remark to the doctor if Gaucher’s disease is suspected. This remark is probably the trigger for a blood test. Gaucher’s disease is not curable. However, it can be treated well with enzyme replacement therapy or substrate reduction therapy. Therefore, once diagnosed, sufferers must make multiple visits to a designated Gaucher center for initiation of appropriate treatment. In addition, regular follow-up examinations are necessary at intervals of three to six months. The necessary examinations should be performed in a clinical Gaucher center. This is also where enzyme replacement therapy is started as infusion therapy. Later, the primary care physician can take over further treatment.

Treatment and therapy

In principle, two forms of therapy are available for Gaucher disease: enzyme replacement therapy (EET) and substrate reduction therapy. Since Gaucher’s disease is caused by an enzyme deficiency, treatment focuses on eliminating this deficiency through enzyme replacement therapy. This involves intravenous infusion of genetically engineered glucocerebrosidase (recombinant imiglucerase). Since the modified enzyme substrate has a relatively long half-life, two-week infusions are sufficient. The substrate is taken up by macrophages and can thus catalyze glucocerebroside degradation. Enzyme replacement therapy is the standard treatment for the non-neuronopathic and chronic neuronopathic forms of Gaucher’s disease and produces a gradual improvement in the symptoms characteristic of Gaucher’s disease.In addition, in a mild course of Gaucher’s disease, a therapeutic approach is pursued in which glucocerebroside accumulation is partially inhibited by the orally administered active substance miglustat (substrate reduction therapy). Due to severe side effects, this drug is only used in patients affected by Gaucher disease for whom enzyme replacement therapy is not indicated. In addition, concomitant measures can be taken to help reduce or eliminate the symptoms in question. For example, severe bone impairment may require additional orthopedic measures, up to and including joint replacement.

Outlook and prognosis

Without treatment, all types of Gaucher disease show a slowly progressive course. With treatment, the prognosis depends on the type of disease present. Gaucher disease type I is generally well treatable with early and timely therapy. In this case, the quality of life is impaired primarily by the bone and joint changes. During childhood, the focus is often on growth disorders as well as bone crises. Some affected persons require a wheelchair after bone fractures (fractures) and necrosis of the femoral head. In Gaucher disease type II (acute neuronopathic form), on the other hand, the prognosis is poor due to the pronounced involvement of the nervous system. Despite therapy, most affected children die within the first two years of life. Gaucher disease type III (chronic neuronopathic form) is treatable, but may be associated with striking mental impairment and limited life expectancy. However, there is not enough data from clinical trials for this type so far, so that a conclusive evaluation is not possible. All patients with Gaucher disease are at increased risk of bleeding complications and splenic ruptures throughout the course of the disease. A definitive cure can only be achieved through gene therapy. Fetal gene therapy for type II has been successfully performed, at least in mice, by British researchers. Whether and when such therapy will be available to Gaucher disease sufferers cannot yet be said.

Prevention

Because Gaucher disease is a genetic lipid storage disorder, it cannot be prevented directly. However, heterozygote testing and prenatal diagnosis can be performed during pregnancy to determine whether the child will be affected by Gaucher disease.

Follow-up

As a genetic disease, Gaucher disease is still incurable. Affected individuals are dependent on taking medication for the rest of their lives. Once patients have been diagnosed and are on therapy, regular follow-up is required to monitor the success of treatment. As a rule, the physician orders the affected person to have blood samples taken once a quarter in order to check the most important values. Depending on the severity of the disease and its course, thorough examinations at a specialized Gaucher competence center are also required every six to twelve months. Depending on the type and stage of the disease, it may cause severe pain and movement disorders and paralysis. Experts advise keeping a pain diary and starting pain therapy to maintain quality of life as much as possible. In addition, exercises that can be easily integrated into everyday life help to improve and maintain the ability to move. In principle, a healthy and balanced diet is also highly recommended for Gaucher syndrome. There is an increased need for calcium and iron. Therefore, dairy products and oatmeal, lentils or broccoli are a valuable part of the diet. If the condition permits, regular exercise is also advisable. However, affected persons should refrain from contact sports, as there is an increased risk of splenic rupture in this disease.

What you can do yourself

Gaucher disease patients can do a lot themselves to improve their quality of life. Actively coping with the disease and taking personal responsibility for managing it, boost self-confidence. Those affected do not fall into a depressive downward spiral as quickly. It is important to accept the disease at first. Rebelling against it only costs unnecessary strength. It is also advisable to research as much as possible about the clinical picture. The more knowledge there is, the less fear and uncertainty there will be.Open questions can be discussed with a trusted physician. It is also advisable to visit a self-help group. In an exchange with other patients, those affected feel understood and no longer so lonely. It is also advisable to seek psychotherapeutic help. A healthy, balanced diet is generally recommended. Patients with Gaucher’s disease can benefit from this in a special way. Calcium strengthens muscles and bones. Iron helps against anemia. Natural foods such as dairy and whole grain products, fish, spinach, nuts and legumes contain many times the nutrients needed. In addition, dietary supplements can be taken to meet daily needs. Of course, only after consulting a doctor. Exercise can also have a positive effect on health. Most sports can be performed without any problems. For safety, the attending physician should be consulted.