Overview of Gaucher Disease

Gaucher disease (pronounced “GO shay” disease) is a genetic condition with a wide range of clinical symptoms affecting several organ systems of the body. In the most common form of Gaucher, people have highly treatable symptoms. In other types of Gaucher disease, symptoms are severe and very difficult to treat. Your healthcare provider will help you learn what to expect in your particular situation.

Causes

Gaucher disease is a genetic disease caused by a problem with a gene called GBA. This gene is part of your DNA, the genetic material you inherit from your parents.

The GBA gene is responsible for making an enzyme called glucocerebrosidase. In people with Gaucher disease, this enzyme is deficient, or it doesn’t work as well as it should.

To understand the importance of this enzyme, it’s important to know about a part of the cell called the lysosome. Lysosomes exist as components inside your body’s cells. They help to clean up and dispose of material that the body is otherwise unable to break down. They perform an important role in breaking down materials that can accumulate in the body. Glucocerebrosidase is one of the enzymes that helps lysosomes do this.

Normally, this enzyme helps recycle a fatty substance in the body called glucocerebroside. But in Gaucher disease, glucocerebrosidase doesn’t work very well. The enzyme might not be active at all, or it may have reduced activity. Because of this, glucocerebroside begins to build up in various areas of the body. This leads to the symptoms of the condition.

When certain immune cells get filled with excess glucocerebroside, they are called “Gaucher cells.” These Gaucher cells can crowd out normal cells, causing problems. For example, the buildup of Gaucher cells in the bone marrow prevents your body from being able to produce the normal amounts of new blood cells there. A buildup of glucocerebroside and Gaucher cells is particularly a problem in the spleen, liver, bone, and brain.

Problems with other types of enzymes in the lysosomes can lead to other types of disorders. As a group, these are called lysosomal storage diseases.

Prevalence

Gaucher disease is a rare condition. It affects roughly one infant born out of 100,000. However, in certain ethnic groups, Gaucher disease is more common, such as in Ashkenazi Jews. For example, about one in 450 infants of this genetic background have Gaucher disease.

Gaucher disease is the most common of the lysosomal storage diseases, which include other conditions such as Tay-Sachs disease and Pompe disease.

Diagnosis

A healthcare provider might first suspect Gaucher disease based on a person’s symptoms and medical signs. If a person is known to have Gaucher disease in their family, that increases suspicion of the disease.

People with Gaucher disease also often have unusual laboratory findings, such as on a bone marrow stain. These findings may be helpful in pointing toward Gaucher. There are a variety of other laboratory and imaging tests that your healthcare provider can use to evaluate the status of your Gaucher. For example, your healthcare provider might want an MRI to check for internal organ enlargement.

However, for a true diagnosis, your healthcare provider will also need a blood test or a skin biopsy. This sample is used to see how well glucocerebrosidase is working. An alternative is a genetic blood or tissue test used to analyze the GBA gene.

Because it is a rare disease, most healthcare providers are not very familiar with Gaucher. Partly because of this, diagnosis of Gaucher disease sometimes takes a while. This is especially likely if no one else in the family is already known to have it.

Types

There are three major types of Gaucher disease: type 1, type 2, and type 3. These types differ somewhat in their symptoms and in their severity. Type 1 is the mildest form of Gaucher. It does not affect the nervous system, unlike type 2 and type 3 Gaucher disease. Type 2 Gaucher disease is the most severe type.

A large majority of people with Gaucher disease have Type 1 disease. About 1 percent of people with Gaucher are thought to have type 2 disease. About 5 percent of people with Gaucher have type 3 disease.

When considering the symptoms of Gaucher disease, it is important to remember that people experience a wide variety of symptom severity. Symptoms overlap between the three types.

Symptoms of Type 1

The signs and symptoms of type 1 Gaucher disease first appear in childhood or adulthood. Bone problems can include:

• Chronic bone pain
• Sudden episodes of bone pain
• Bone fracture
• Osteoporosis
• Arthritis

Type 1 Gaucher also affects some of the internal organs. It can cause enlargement of the spleen and liver (called hepatosplenomegaly). This is usually painless but causes abdominal distension and a feeling of fullness.

Type 1 Gaucher also causes something called cytopenia. This means that people with Gaucher disease have lower than normal levels of red blood cells (causing anemia), white blood cells, and platelets. People with Gaucher may have other coagulation and immune abnormalities as well. This can lead to symptoms like :

• Fatigue
• Easy bleeding or bruising
• Nosebleeds
• Increased risk of infection

Gaucher disease can also affect the lungs, leading to such problems as:

• Interstitial lung disease
• Pulmonary hypertension
• Cough
• Shortness of breath

Additionally, type 1 Gaucher can cause:

• Increased risk of gallstones
• Poor growth and development
• Psychological complications, such as depressed mood
• Heart complications (rare)
• Kidney complications (rare)

Some people who have type 1 Gaucher disease have very mild disease and might not notice any symptoms. However, clinicians can detect slight abnormalities with the help of laboratory findings and imaging tests.

Symptoms of Type 2 and 3

Almost all the same systems of the body affected by type 1 disease can also cause problems in type 2 and type 3 disease. However, types 2 and 3 also have additional neurological symptoms. These symptoms are most severe in patients with type 2 disease. These children usually die before age 2. In a very rare form of the disease, children die shortly before or shortly after birth. In people with type 3 Gaucher, these problems are not as severe, and people may live into their 20s, 30s, or longer.

Neurological symptoms seen in type 2 and type 3 disease many include:

• Eye misalignment (strabismus)
• Problems with tracking objects or shifting gaze
• Seizures
• Muscle rigidity
• Muscle weakness
• Problems with balance and coordinated movement
• Problems with speech and swallowing
• Mental retardation
• Dementia

A subset of people with type 2 or type 3 Gaucher also have additional symptoms. Examples include skin changes, problems with their cornea, and heart valve calcification.

Secondary Diseases

Gaucher disease also increases the risk of some other diseases. For example, people with Gaucher have a higher than average risk of Parkinson disease. Certain cancers may also be more common in people with Gaucher disease, including:

• Blood cancers
• Multiple myeloma
• Liver cancer
• Kidney cancer

People with Gaucher also are also at risk of some secondary complications, such as splenic infarction (lack of blood flow to the spleen, causing tissue death and severe belly pain).

Treatment

The standard of treatment of Gaucher disease is enzyme replacement therapy (sometimes called ERT). This treatment revolutionized the treatment of Gaucher.

In ERT, a person receives an artificially synthesized form of glucocerebrosidase in the form of an intravenous infusion. Different forms of ERT are now on the market commercially, but they all provide replacement enzyme. These are:

• imiglucerase (trademarked as Cerezyme)
• velaglucerase alfa (VPRIV)
• taliglucerase alfa (Elelyso)

These treatments are very effective at reducing bone symptoms, blood problems, and liver and spleen enlargement. However, they don’t work very well at improving the neurological symptoms seen in type 2 and type 3 Gaucher disease.

ERT is very effective at reducing symptoms of type 1 Gaucher, and at reducing some of the symptoms of type 3 Gaucher. Unfortunately, because type 2 Gaucher has such severe neurological problems, ERT is not recommended for this type. People with type 2 Gaucher usually receive supportive treatment only.

Another newer treatment option for type 1 Gaucher is substrate reduction therapy. These drugs limit the production of substances that glucocerebrosidase breaks down. These are:

• miglustat (Zavesca)
• eliglustat (Cerdelga)

Miglustat is available as an option for people who can’t take ERT for some reason. Eliglustat is an oral drug that is an option for some people with type 1 Gaucher. It is a newer drug, but some evidence suggests that it is as effective as ERT therapies.

These treatments for Gaucher can be very expensive. Most people will need to work closely with their insurance company to see that they can get adequate coverage of the treatment. 

People with Gaucher disease should be treated by a specialist with experience with the condition. These people need regular follow up and monitoring to see how well their disease is responding to treatment. For example, people with Gaucher often need repeated bone scans to see how the disease is affecting their bones. 

People who are not able to receive ERT or a newer substrate reduction therapy may need additional treatments for the symptoms of Gaucher. For example, these people might need blood transfusions for severe bleeding.

Genetics

Gaucher disease is an autosomal recessive genetic condition. That means that a person with Gaucher disease gets a copy of an affected GBA gene from each parent. A person who has just one copy of an affected GBA gene (inherited from one parent) is said to a carrier of the condition. These people have enough functioning glucocerebrosidase that they don’t have symptoms. Such people often do not know that they are disease carriers unless someone in their family is diagnosed with the disease. Carriers are at risk of passing on an affected copy of the gene to their children.

If you and your partner both are carriers for Gaucher disease, there is a 25 percent chance that your child will have the disease. There is also a 50 percent chance that your child will not have the disease but will also be a carrier for the condition. There is a 25 percent chance that your child will neither have the disease nor be a carrier. Prenatal testing is available in cases where the child is at risk for Gaucher.

Talk to your healthcare provider if you worry that you might be a carrier of Gaucher disease based on your family history. If someone in your family has Gaucher disease, you may be at risk. Genetic tests can be used to analyze your genes and see if you are a disease carrier.

A Word From Verywell

It can be overwhelming to learn that you or a loved one has Gaucher disease. There is a lot to learn about managing the condition, and you don’t have to do it all at once. Fortunately, since the availability of ERT, many people with Gaucher disease can lead relatively normal lives.