Gaucher Disease: What You Need to Know About This Rare Genetic Disorder

Gaucher disease (pronounced go-shay) is a rare genetic disorder that is passed down from parents to children. Globally, in the general population, it affects up to 1 in 40,000 newborns. However, this disorder is most common in the Ashkenazi Jewish population (those with Eastern European ancestry), affecting approximately 1 in 850 people [1]. Gaucher disease can significantly impact your quality of life by causing anemia, belly pain, bone pain, lung problems, etc. Unfortunately, this disorder is not curable. However, with the help of modern medicine, you can manage symptoms and lead a more fulfilling life.

What Is Gaucher Disease?

Gaucher disease is a genetic disorder that is caused by a mutation of an enzyme called glucocerebrosidase. This enzyme is responsible for breaking down a fatty substance called glucocerebroside. When this enzyme is missing or doesn’t work properly, glucocerebrosides build up in your bone marrow and certain organs, such as the spleen and liver, instead of being broken down. This leads to many symptoms and complications. Your liver and spleen become enlarged and don’t work properly. This disease can also affect your lungs, brain, eyes, etc [2].

Types of Gaucher Disease

There are three main types of Gaucher disease. They have different symptoms and severity levels [2]:

Type 1: This is the most frequent form of the disease in the U.S., and accounts for more than 90% of all cases. Gaucher disease type 1 can cause symptoms like enlarged spleen and liver, bone pain and fractures, and fatigue. You may also experience anemia and low platelet count, causing easy bruising. This form of the disease doesn’t affect your brain or spinal cord. Your symptoms can start at any age, and these symptoms range from mild to severe. There is no cure, but with proper treatment, you can have a normal lifespan.

Type 2: This is the most severe and rare form of the disease, usually affecting babies aged 3 to 6 months. It causes irreversible brain damage. Unfortunately, currently there is no treatment for this form of the disease. Babies affected by this condition usually die within 2 to 3 years.

Type 3: The severity of this type of Gaucher disease is between type 1 and type 2. Worldwide, this is the most common type of Gaucher disease, but it is rare in the U.S. and Europe. The symptoms may begin in early childhood or adolescence. It causes similar symptoms to type 1. It also causes some neurological (brain) symptoms, including seizures, that are milder than those of type 2 but become more progressive over time. People with Type 3 Gaucher disease usually have a shorter lifespan. With proper treatment, they can live into adulthood.

What Causes Gaucher Disease?

Gaucher disease is a genetic disorder that you inherit from your parents. All types of the disease are caused by mutations (changes) in the GBA1 gene [3]. This gene tells your body to make an enzyme called glucocerebrosidase. 

This enzyme helps to break down a fatty substance (sphingolipid) called glucocerebroside. Normally, this fatty substance is found in the walls of your cells. People with Gaucher disease have either a mutation or a lack of this enzyme. As a result, the fatty substances don’t get broken down properly. Rather, they accumulate inside certain white blood cells, which are in charge of eating up the waste products of dead cells. 

These white blood cells with built-up fat are called Gaucher cells. They gather in various organs, including the spleen, liver, bone marrow, and brain. This causes a wide range of symptoms.

To get the disease, a person needs to inherit the defective gene from both parents [4]. This form of genetic inheritance is referred to as “autosomal recessive.” But if you inherit it from only one parent, you will become a carrier of the disease, but will not develop any symptoms.

Symptoms

The symptoms of Gaucher disease greatly vary from person to person, depending on the type and severity. Some people with Type 1 Gaucher disease may not show symptoms until later in life, while others may experience them in childhood.

There are some common symptoms that appear in all types of Gaucher disease, while neurological symptoms appear only in Type 2 and Type 3 [2]. These symptoms are given below:

Common Symptoms 

These symptoms can appear in all types of Gaucher disease. For some people, these symptoms are mild, while for others they may be severe. These symptoms include:

Anemia: You may experience a low red blood cell count, causing fatigue and weakness.

Low Platelet Count: People with this disease experience easy bruising and bleeding because of a low platelet count.

Lung Problems: You may experience difficulty breathing because fatty substances may build up in your lungs.

Bone Pain and Fracture: You may experience bone pain, joint pain, and damage. This disease can also cause osteoporosis, a condition where your bone mass becomes weak and brittle, increasing the likelihood of fractures. 

Enlarged Organs: In Gaucher disease, your spleen and liver can become enlarged due to fat buildup. This causes symptoms like stomach pain, easy bruising or bleeding, tissue damage in the liver or spleen, etc.

Neurological Symptoms

In addition to the common symptoms, people with Gaucher disease type 2 and type 3 also develop neurological symptoms [5]. These symptoms are usually more severe in type 2 patients, and they usually pass away by age 2. These symptoms include:

• Eye movement problems
• Seizures
• Poor coordination
• Brain damage
• Cognitive decline (memory loss, reduced thinking skills and mental capabilities)

Diagnosis

Diagnosing Gaucher disease starts by analyzing your symptoms and doing some laboratory tests. If you develop symptoms like enlarged spleen, low platelet and red blood cell count, or neurological problems, your doctor may suspect Gaucher disease. To confirm the diagnosis, the following tests are done [5][6]:

Enzyme Activity Test: A blood test called beta-glucosidase leukocyte (BGL) test is done to measure the activity of the enzyme glucocerebrosidase. If you have a low level of this enzyme activity, it might suggest that you may have Gaucher disease.

Genetic Test: This test is done to identify mutations (changes) in the GBA gene. It is one of the most reliable ways to confirm the diagnosis.

Bone Marrow Biopsy: A small sample is taken from your bone marrow to look for Gaucher cells. Nowadays, however, this test is less common because genetic and enzyme tests are usually enough.

Blood Tests: Your doctor may perform some blood tests to check for anemia, low platelet count, etc.

Imaging Tests: An MRI or ultrasound test can show if your liver, spleen, or bones are affected.

Prenatal Testing: Before birth, a prenatal test can diagnose Gaucher disease in the fetus.

Sự đối đãi

Thanks to modern medicine, there are some effective treatment options for Type 1 and Type 3 Gaucher disease. Sadly, there is still no treatment for type 2, and none of the types have a complete cure. The goal of the treatment options is to reduce symptoms and improve quality of life. Here are some treatment options for Gaucher disease [1][2][5]:

Enzyme Replacement Therapy (ERT): This is the standard treatment for Type 1 and Type 3 Gaucher disease patients. In this therapy, you receive a man-made form of the missing enzyme (glucocerebrosidase) via intravenous infusion every 2 weeks. ERT helps to reduce spleen and liver size, improve blood counts, and relieve bone pain. However, it is not effective for neurological symptoms.

Substrate Reduction Therapy (SRT): This therapy works differently from ERT. It is an oral medication that reduces the amount of glucocerebroside produced in your body. 

Supportive Care: Gaucher disease affects multiple organs and causes many symptoms. To manage these symptoms, doctors recommend some supportive care, such as:

• Blood transfusions for severe anemia or bleeding.
• Orthopedic surgery for joint damage.
• Bone marrow transplants to help with blood cell production.
• Medicines to manage pain.
• Physical therapy to improve movement and strength.

FAQs

Here are some common frequently asked questions about Gaucher disease:

1. Is Gaucher Disease Fatal?

It depends on the type [2]. Type 1 Gaucher disease is usually not fatal. With proper treatment, you can have a near-normal lifespan. Type 2 is the most severe form and is fatal. Babies affected by this condition usually pass away within 2 to 3 years. Type 3 patients have a reduced lifespan. Most of them survive till early adulthood.

2. Can Gaucher Disease Affect Fertility or Pregnancy?

Gaucher disease doesn’t directly cause infertility, but it can cause some problems during pregnancy. Women with the disease may experience complications such as anemia, thrombocytopenia (low platelet count), and bleeding, especially during pregnancy and delivery [7]. So, it is recommended to plan your pregnancy under the guidance of a medical team.

3. What is the Cost of Treatment for This Disease?

Treatment — especially enzyme replacement therapy — is very expensive, often costing U.S. $200,000 per year [1]. However, many countries have insurance coverage, government programs, or patient assistance foundations that help reduce or cover the cost.