FAQs

Gaucher disease is a genetic condition caused by a deficiency (not having enough) of the enzyme glucocerebrosidase (GBA)^1. This enzyme deficiency is caused by changes in the GBA gene (also called a mutation) and when the enzyme is deficient, it leads to buildup (storage) of certain lipids (fats) called glucocerebrosides (GL-1) in the spleen, liver, bone marrow, and other parts of the body.¹ Each gene is a recipe for a making a certain protein, enzymes are types of proteins that help speed up chemical reactions in the human body. In the case of Gaucher disease, glucocerbrosidase enzyme metabolizes fats called glucorebrosides. Symptoms of the disease may include enlargement of the spleen and liver (a big belly or abdomen), anemia (low amount of red blood cells), thrombocytopenia (low platelet counts), bone pain, and bone fragility².

Type 1 The most common type of the disorder that impacts the body rather than the brain.²
Type 2 An early acute onset, very severe type of Gaucher disease that affects the body and brain.²
Type 3 A variable chronic type of the condition that affects the body and often the brain.²

Some of the other names used for Gaucher disease include:

• Gaucher splenomegaly
• Glucocerebrosidase deficiency
• Glucocerebrosidosis
• Glucosylceramidase deficiency
• Acid β-glucosidase deficiency

Gaucher disease is seen in people around the world. Type 1 Gaucher disease is estimated to be in 1: 40,000 to 1:60,000 individuals around the world.¹ It is more commonly seen in individuals of Ashkenazi Jewish Spanish, Portuguese, Swedish, Greek, and Albanian descent.¹ Types 2 and 3 Gaucher disease is estimated to occur in 1 in 100,000 - 300,000 births.²

Gaucher disease is classified into three types. Type 1 is the most common form of Gaucher disease, representing about 95% of Gaucher disease patients.¹ It impacts the body rather than the brain (non-neuronopathic). Type 2 Gaucher disease is the early onset, very severe and acute type of Gaucher disease that affects the body and brain (neuronopathic). This is the most severe type of Gaucher disease.² Type ³ Gaucher disease is a variable and more chronic form of the condition that affects the body and often the brain (neuronopathic).² Neuronopathic is a term physicians use that describes 'affecting the brain'. When a patient is diagnosed with Gaucher disease, the doctor can do genetic testing that tells them which type of Gaucher disease is most likely affecting them.

Age of onset and symptoms are variable in type 1 Gaucher disease; some affected individuals can present with signs of Gaucher in childhood, and others may be well into their later years or never become symptomatic at all.¹ As a general rule, the younger the presentation, the more severe the disease. Symptoms of the disease may include enlargement of the spleen and liver (a big belly or abdomen), anemia (pale skin and easily tired), thrombocytopenia (low platelet counts causing easy bruising and bleeding like nosebleeds), bone pain (resulting in bones that break and damage easily), and bone fragility (osteoporosis).¹

Type 2 Gaucher disease is the most severe of the three types of Gaucher disease. It involves severe neurological symptoms in newborn babies like seizures (abnormal electrical activity in the brain) and unusual eye movements. Affected individuals have significantly shortened life span. Death usually occurs by age 2-3 years of life.¹ Treatment is usually not effective to help the brain and nervous symptoms seen in type 2 Gaucher disease, although it can help improve blood levels and the size of the liver and spleen^.2

In type 3 Gaucher disease, symptoms usually develop in childhood. Symptoms of the disease may include enlargement of the spleen and liver (a big belly or abdomen), anemia (pale skin and easily tired), thrombocytopenia (low platelet counts causing easy bruising and bleeding like nosebleeds), bone pain (resulting in bones that break and damage easily), and bone fragility (osteoporosis).¹ They may also have neurological symptoms like seizures (abnormal electrical activity in the brain), ataxia (loss of control of movement), and abnormal eye movements.¹ Children with type 3 disease often blink excessively and have difficulty moving their eyes from side to side without thrusting their head to keep up with an object.¹

Pathogenic variants, also called mutations, (change in DNA that causes disease) in the GBA gene cause Gaucher disease.1 The GBA gene is located on chromosome 1 on the long arm at region 2 band 1 (1q21).¹ There are 300 different disease causing mutations that have been discovered in the GBA gene.²

Different genetic mutations or pathogenic variants (change in DNA that causes disease) in in the GBA gene may lead to differences in severity and presentation of Gaucher disease, though the correlation is often imperfect^.1 At present other genetic factors that influence disease severity or progression are not understood.

In general, affected individuals who have two copies of a GBA mutation such as N370S or R120W variants tend to have milder disease than those who have one copy of the N370S or R120W mutation and another mutation- but this is a general rule of thumb and not a fact.2 Individuals with at least one copy of the N370S or R120W mutation have type 1 Gaucher disease.¹ Individuals who have two copies of mutations called L444P or RecNciI tend to have severe disease, often with neuronopathic complications (i.e., types 2 and 3 Gaucher disease)^.2 When a patient is diagnosed with Gaucher disease, the doctor can do genetic testing to identify the pathogenic variants (change in DNA that causes disease) in the GBA gene to determine which type of Gaucher disease is most likely affecting the patient.

The main signs and symptoms of Gaucher disease are:

• Enlarged spleen and/or liver (big belly)
• Anemia (low amount of red blood cells) causing fatigue
• Easy bruising and bleeding (due to low platelet count)
• Bone pain or weakness
• Breathing problems/pulmonary disease in some people

Individuals living with type 2 or 3 Gaucher disease will have these symptoms plus other medical issues such as seizures (abnormal electrical activity in the brain) or abnormal eye movements.

Common health problems in patients with type 1 Gaucher disease are:

• Bone Pain/Bone crisis (episode of severe pain in the bone)
• Hepatosplenomegaly (enlarged spleen and/or liver [big belly])
• Anemia (low amount of red blood cells) causing easy fatigue
• Thrombocytopenia (low platelet counts causing easy bruising and bleeding)
• Osteopenia/Osteoporosis (brittle bones)

The signs and symptoms seen in type 2 and 3 Gaucher disease, but not type 1, are:^1,2

• Seizures (abnormal electrical activity in the brain) and cognitive impairment (trouble remembering things, concentrating, or making decisions, early memory loss)
• Muscle stiffness
• Strabismus (crossed eyes)
• Ocular motor apraxia (a problem with side-to-side (horizontal) eye movements
• Loss of coordination and balance
• Ataxia (loss of control of movement)
• Breathing difficulties

All forms of Gaucher disease are inherited in an autosomal recessive pattern. This means that both copies of a person’s GBA gene must have mutations or pathogenic variants (change in DNA that causes disease) for an individual to have the condition.¹ The parents of an individual with Gaucher disease each carry one non working copy of a GBA gene and one standard working copy of the GBA gene.¹ If both parents carry one copy of a GBA gene with a mutation or pathogenic variant, there is a 1 in 4 or 25% chance that each of their children will have Gaucher disease, a 2 in 4 or 50% chance for them to be carriers (person who has one genetic change associated with a disease that can pass it on to their child, but may not have symptoms themselves), and a 1 in 4 or 25% chance for them to have two working copies of the GBA gene.

Carriers of Gaucher disease do not have the medical issues seen with the condition. The fact that an individual is a carrier only becomes important if their partner is also a carrier and they have a pregnancy together.¹ In that case, there is a chance (up to 25%, or 1 in 4) that the baby may be born with Gaucher disease.

Having said this, although carriers (person who has one genetic change associated with a disease) that can pass it on to their child, but may not have symptoms themselves) for Gaucher disease are not at increased risk to have Gaucher disease, they may be at increased risk to develop symptoms of Parkinson disease (a condition that affects movement and often includes tremors or shaking).

Testing for Gaucher disease often begins when a doctor orders Gaucher testing and directs their patients to their local hospital or clinic to have blood drawn. The laboratory sends a sample to a specialized testing laboratory to determine the levels of β-glucosidase or glucocerebrosidase enzyme. If enzyme levels are low, genetic testing of the GBA gene looking for disease-causing genetic changes should be done next. Medical geneticists have expert knowledge of the management, monitoring, and treatment of people with Gaucher disease. In order to be tested for Gaucher disease, patients and families can ask their doctor to test them or refer them to a Gaucher expert.

In some countries, parents can choose to have their babies tested for Gaucher disease on their newborn blood test.^1,2 This is not available in every country. To learn more about newborn testing options, patients and families can ask their doctor.

An enzyme test on blood to determine the amount of glucocerebrosidase in a person is the standard method for diagnosing Gaucher disease. Affected individuals with type 1 Gaucher disease typically have 20% of the normal enzyme level compared with unaffected individuals. Type 2 and type 3 children usually have less residual enzyme (~0-15%) activity compared with unaffected individuals.

The following medical tests are commonly conducted in patients with Gaucher disease:

• Blood tests to monitor blood cells and platelets
• Bone marrow examination
• Radiographic studies of the bone/Bone density scan
• Scan to measure size of liver and spleen (MRI/CT)

Bone marrow examinations in patients with Gaucher disease often reveal the presence of lipid-engorged macrophages (immune cells), characterized by a fibrillary, 'crumpled silk' appearance to the cytoplasm (liquid part of a cell) and an eccentrically placed nucleus^.1 This material also stains positively with periodic acid-Schiff (PAS) reagent.² Although a bone marrow examination can suggest someone has Gaucher disease, it is not necessary, as an enzyme test on blood to determine the amount of glucocerebrosidase in a person is the standard method for diagnosing Gaucher disease.³

Enzyme testing is not reliable for carrier testing because there is an area of overlap in enzyme levels between non-carriers and carriers (person who has one genetic change associated with a disease that can pass it on to their child, but may not have symptoms themselves). Genetic testing is done to identify carriers for Gaucher disease. The test will look for mutations in the GBA gene. Usually the GBA test is called sequencing and looks for all the DNA bases in the GBA gene.

Gaucher disease has several approved treatments. One treatment available for Gaucher disease is enzyme replacement therapy (ERT).1 ERT is given to replace the missing enzyme in Gaucher disease.¹ Substrate reduction therapy (SRT) is also an approved therapy option depending on the patient’s age.¹ Unfortunately, no therapy is yet available that crosses the blood-brain barrier so no treatment is capable of fixing the neurological symptoms found in types 2 and 3 Gaucher disease.²

Enzyme replacement therapy (ERT) works by providing the body with synthetic (artificial/man-made) enzyme to clear the stored waste product (fat) that has built up in the body's cells (the lysosome) causing the symptoms of Gaucher disease.

Substrate reduction therapies (SRT) are oral medications that work by reducing the amount of fat (GL-1 substrate) made by the body that will eventually be turned into waste products. The goal is to limit the fat buildup (GL-1) to a level that can be effectively cleared by the naturally occurring enzyme with residual activity.

Symptom based treatments for Gaucher disease depend on the type of Gaucher disease affecting the patient. Some treatment common to all three types include:

• Analgesics for bone pain
• Joint replacement surgery for relief from chronic pain and restoration of function
• Bisphosphanates and calcium for osteoporosis
• Prophylactic antibiotics
• Blood transfusions

Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in individuals with moderate to severe low platelets (thrombocytopenia) as they can increase the risk for free bleeding.

The easiest way to learn more about studies and clinical trials in Gaucher disease is to talk to a doctor that specializes in Gaucher disease. In order to find an expert with Gaucher disease, patients and families can ask their doctor to refer them to a Gaucher expert.

The easiest way to learn about clinical trials in Gaucher disease open for people to join is to talk to a doctor that specializes in Gaucher disease. In order to find an expert with Gaucher disease, patients and families can ask their doctor to refer them to a Gaucher expert.

A cure for Gaucher disease would be a one-time treatment that would prevent all medical issues related to Gaucher disease. Currently, there are long-term treatments for Gaucher disease, but not a cure.¹

Treatments are being studied to address the underlying causes of Gaucher disease that may someday lead to a cure or at least put the disease "into remission". These treatments include gene therapy, which could add or replace the non working GBA genes in Gaucher patients and help the body make its own enzyme.¹ Other research includes a gene editing technology called CRISPR that would act as a "spellcheck" and correct the changes or mutations in the non working GBA gene to a working one.²

In order to learn more about treatment and studies looking into a cure for Gaucher disease, patients and families can ask their doctor to refer them to a Gaucher expert.

Many women with Gaucher can and do become pregnant and have healthy babies. However, since pregnancy may affect the course of Gaucher disease, it is important to talk to a physician prior to getting pregnant (or as soon as they become aware they are pregnant) about how to best manage pregnancy.¹ Pregnancy can worsen pre-existing Gaucher symptoms and may trigger new features such as bone pain. Women with severe thrombocytopenia and/or clotting (clump of blood traveling in the body) abnormalities may have an increased risk of bleeding around the time of delivery.² Accordingly, working closely with a high-risk obstetrician (doctor who specializes in pregnancy) maximizes the best outcomes for the mother and baby while managing any issues that arise.

The precise risk for individuals with Gaucher disease of developing Parkinson disease (a condition that affects movement and often includes tremors or shaking) is not known, but has been variously estimated as 20- to 30-fold the risk of an individual in the general population^.1

GBA mutations have been identified in 5%-10% of individuals with Parkinson disease (a condition that affects movement and often includes tremors or shaking).² Parkinson disease associated with Gaucher disease is indistinguishable from other Parkinson disease, although Parkinson disease associated with Gaucher disease has a slightly earlier onset (~5 years earlier) and more frequent cognitive dysfunction.³

Carriers (person who has one genetic change associated with a disease that can pass it on to their child, but may not have symptoms themselves) for Gaucher disease are generally healthy. Family studies suggest that carriers for Gaucher disease are at increased risk for Parkinson disease (a condition that affects movement and often includes tremors or shaking).