What is Gaucher disease? Diagnosis, symptoms, and treatment

Gaucher disease (GD) is classified as an ultra-rare, blood storage disorder . There are currently approximately 100 patients diagnosed with Gaucher disease in Poland, but there may be many more who remain undiagnosed. Diagnosis is challenging, as the symptoms can suggest other diseases, such as blood cancers.

In this article, we will take a closer look at how to recognize Gaucher disease, what its symptoms are, and how the treatment process works.

What is Gaucher disease?

GD is caused by a mutation in the GBA gene , which significantly reduces the activity of an enzyme called glucocerebrosidase, which is necessary for, among other things, the breakdown of cell membrane glycosphingolipids. This leads to the accumulation, or storage, of glucocerebroside in macrophages. Such macrophages are called Gaucher cells .

Their accumulation in the spleen, liver and bone marrow results in the typical clinical symptoms of this disease. 

Symptoms of Gaucher disease

Gaucher disease affects many organs and tissues of the human body, and symptoms can vary significantly between patients. Some patients with a mild form may not experience symptoms until old age. For others, symptoms can become life-threatening even in childhood. The symptoms of Gaucher disease result from the accumulation of fatty substances in internal organs and bones. The most common sites of accumulation are the liver, spleen, and bone marrow. 

Typical symptoms, almost always present in adults with type I Gaucher disease, include : weakness, fatigue, increased tendency to bleed (nosebleeds, gum bleeding, subcutaneous bruising, heavy menstrual bleeding), bone pain and pathological bone fractures, osteonecrosis (most often of the hip joints), enlargement of the spleen and liver .

• An enlarged spleen breaks down red blood cells faster than they are produced, which can lead to anemia , resulting in a lack of energy and frequent fatigue . An enlarged spleen can also cause thrombocytopenia , which increases the tendency to bleed and bruise .
• Furthermore, Gaucher disease is associated with coagulation disorders of complex etiology. Patients may have decreased levels of coagulation factors II, V, VII, VIII, IX, X, XI, XII, and fibrinogen. All of these factors contribute to an increased risk of bleeding during dental procedures, childbirth, and major surgical procedures.
• Another symptom is a decrease in white blood cells due to excessive filtering by the enlarged spleen. This reduction can reduce the body's ability to fight infection .
• Bone pain is a common symptom. This is caused by abnormal bone formation, making bones more brittle and susceptible to infection. This increases the risk of frequent fractures and mobility problems.

Gaucher disease diagnosis

Gaucher disease can be accurately diagnosed with a simple blood test, the "dry spot test," which measures the activity of the enzyme glucocerebrosidase .
A dry spot test of 30% or less definitively confirms Gaucher disease. A second test measures elevated activity of the enzyme chitotriosidase, which measures glucocerebroside storage in macrophages.

During the diagnosis of Gaucher disease, doctors may order a number of other tests:

• performing magnetic resonance imaging or computed tomography to view changes in the liver and spleen,
• radiological diagnostics to assess bone changes,
• ECG, echocardiogram to assess heart function, neurological diagnostics for damage to the central nervous system and peripheral nerves.

Gaucher disease should be diagnosed especially in people with an enlarged spleen and liver, anemia, thrombocytopenia and bone pain.

Unfortunately, it often takes many months or even years for a person with Gaucher disease to receive a correct diagnosis. 

Treatment of Gaucher disease

The primary treatment for Gaucher disease is enzyme replacement therapy (ERT ), which involves administering synthetic glucocerebrosidase to patients, thereby promoting the proper breakdown of glucosylceramide. An alternative substrate restriction therapy has also been developed, which inhibits the formation of glucosylceramide in the body.

In addition to causal treatment, it is also advisable to use various methods of symptomatic treatment, e.g. painkillers in the case of bone pain or surgical decompression in the case of compression of the nervous system structures. 

Treatment of the underlying cause usually leads to a significant reduction in spleen volume and normalization of blood . Occasionally, partial or total splenectomy may be considered in cases of significant splenomegaly, splenic infarcts, and/or extreme thrombocytopenia despite treatment of the underlying cause.

Gaucher disease is a complex genetic disorder that requires appropriate diagnosis and treatment. Modern therapies, such as enzyme replacement therapy, allow patients to lead normal lives despite their chronic illness. Early detection and treatment are crucial to avoiding serious complications, such as bone, liver, or lung damage. Regular testing and specialist care are essential in managing this condition.

If you suspect symptoms in yourself or a loved one suggestive of Gaucher disease, it's important to take appropriate diagnostic steps as soon as possible. The basic test for an accurate diagnosis of Gaucher disease is the Dried Blood Spot Test, which is available free of charge at the Luxmed Clinic. You can book an appointment online or by phone at 81 532 37 11.

The study is intended for patients aged 18 and over.

Marta Morawska, MD, PhD 

Hematologist, Internal Medicine Specialist