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 and when the enzyme is deficient, it leads to buildup (storage) of a lipid (fat) called glucocerebrosides (GL-1) in the spleen, liver, bone marrow, and other parts of the body.¹ Symptoms of the disease may include enlargement of the spleen and liver (a big belly or abdomen), anaemia, thrombocytopenia (low platelet counts), bone pain, and bone fragility².

Gaucher disease encompasses a wide spectrum of signs and symptoms. There are 3 different types of the Gaucher disease²:

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

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 world¹. It is more commonly seen in individuals of Ashkenazi Jewish Spanish, Portuguese, Swedish, Greek, and Albanian descent¹. Types 2 and 3 Gaucher disease is estimated to occur in 1 in 100,000 - 300,000 births².

Gaucher disease is classified into three types. Type 1 is the most common form of Gaucher disease, representing about 95% of Gaucher disease patients¹. It impacts the body rather than the brain (non-neuronopathic). Type 2 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 disease². Type 3 is a variable and more chronic form of Gaucher disease that affects the body and often neuronopathic (affecting the brain) ². 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 disease in childhood, and others may be well into their later years or never become symptomatic at all¹. As a general rule, earlier onset of symptoms indicates increasing severity of 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 (as the result of bones that break and damage easily), and bone fragility (osteoporosis) ¹.

Type 2 Gaucher disease is the most severe type of Gaucher disease. It involves severe neurological symptoms in newborn babies like seizures and unusual eye movements. Affected individuals have significantly shortened life span. Death usually occurs by age 2-3 years of life¹. 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 spleen².

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 (as the result of bones that break and damage easily), and bone fragility (osteoporosis) ¹. They may also have neurological symptoms like seizures, ataxia (an unsteady, staggering walk), and abnormal eye movements¹. 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 a moving object¹.

Pathogenic variants (also called mutations) in the GBA gene cause Gaucher disease¹. 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 gene².

Different genetic mutations or pathogenic variants in the GBA gene may lead to differences in severity and presentation of Gaucher disease, though the correlation is often imperfect¹. 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 only a general rule of thumb². Individuals with at least one copy of the N370S or R120W mutation have type 1 Gaucher disease¹. Individuals who have two copies of mutations called L444P or RecNciI (L444P +. A456P + V460V) 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 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
• Anemia causing fatigue
• Easy bruising and bleeding (due to low platelet count)
• Bone pain or weakness (osteopenia, osteonecrosis, bone crisis)
• 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 or abnormal eye movements.

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

• Bone pain/Bone crisis
• Hepatosplenomegaly (large liver and spleen)
• Anemia (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 and cognitive impairment
• Muscle stiffness
• Strabismus (crossed eyes)
• Ocular motor apraxia (a problem with side-to-side (horizontal) eye movements)
• Loss of coordination and balance
• Ataxia (unsteady, staggering walk)
• 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 for an individual to have the condition¹. The parents of an individual with Gaucher disease each carry one non-working copy and one working copy of the GBA gene¹. If both parents carry one copy of a GBA gene with a mutation or pathogenic variant, there is a 1 in 4 (25%) chance that each of their children will have Gaucher disease, a 2 in 4 (50%) chance for them to be carriers, and a 1 in 4 (25%) chance for them to have two working copies of the GBA gene.

Carriers of Gaucher disease do not have the medical issues associated 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 together¹. In that case, there is a chance (up to 25%, or 1 in 4) that the baby may be born with Gaucher disease.

However, although carriers 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 doctor would initiate Gaucher disease testing by directing their patients to local hospitals or clinics to have their blood drawn. The laboratory sends a sample to a specialized testing laboratory to determine the levels of GBA 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 disease 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 to determine the amount of GBA in a person's blood 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 ('Gaucher cells'), characterized by a fibrillary, 'crumpled silk' appearance to the cytoplasm and an eccentrically placed nucleus¹.This material also stains positively with periodic acid-Schiff (PAS) reagent². Although a bone marrow examination can suggest someone has Gaucher disease, it is not definitive. An enzyme test to determine the amount of GBA in a person's blood is still the preferred method for diagnosing Gaucher disease³.

Enzyme testing is not reliable to identify a carrier because there is an area of overlap in enzyme levels between non-carriers and carriers. 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.

If the GBA gene mutations (pathogenic variants) in a family are known, prenatal testing may be considered. Testing in the pregnancy involves examining the baby's GBA gene to determine if they have the known family mutations. Before birth, the baby's genetic material can only be collected by invasive procedures, such as chorionic villi sampling or amniocentesis.

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 GBA enzyme in Gaucher disease¹. Substrate reduction therapy (SRT) is also an approved therapy option depending on the patient's age¹. 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) made by the body that will eventually be turned into waste products. The goal is to limit the GL-1 buildup 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 treatments 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 of 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. 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. 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 resolve all medical issues related to Gaucher disease. Currently, long-term treatments are available for Gaucher disease, but not a cure¹.

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 GBA¹. 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 one².

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 that they are pregnant) about how to best manage pregnancy¹. Pregnancy can worsen pre-existing Gaucher symptoms and may trigger new symptoms such as bone pain. Women with severe thrombocytopenia and/or clotting abnormalities may have an increased risk of bleeding around the time of delivery². Thus, it is important to work closely with a high-risk obstetrician to maximize the best outcomes for the mother and baby while managing any issues that may arise.

The precise risk for individuals with Gaucher disease of developing Parkinson disease is not known, but has been variously estimated as 20- to 30-fold the risk of an individual in the general population¹.

GBA mutations have been identified in 5%-10% of individuals with Parkinson disease². Gaucher disease-associated Parkinson disease is indistinguishable from other Parkinson disease, although Gaucher disease-associated Parkinson disease has a slightly earlier onset (~5 years earlier) and more frequent cognitive dysfunction³.

Carriers for Gaucher disease are generally healthy. Family studies suggest that carriers for Gaucher disease are at increased risk for Parkinson disease.