Gaucher disease

Except in families in which a previously affected sibling had neurologic disease (i.e., types 2 or 3), it is not possible to be certain of the severity of the disease in a pregnancy at risk. Individuals with GD with acute neurologic disease (i.e., type 2) tend to have a similar disease course. However, it should be noted that individuals with Gaucher disease and chronic neurologic involvement (i.e., type 3) could show variable rates of disease progression, even when they are members of the same family.

Only if your partner is also a carrier for Gaucher disease can your children develop the condition. In that case, there is a 50% chance for each of your children to have Gaucher disease. If your partner is not a carrier for Gaucher disease, none of your children will have Gaucher disease.

Although Gaucher disease can be seen in people from all backgrounds and ethnicities, it is more common in the Ashkenazi Jewish population. It is estimated that type 1 Gaucher disease affects about 1 in 855 individuals of Ashkenazi Jewish background. Approximately 1:18 persons of Ashkenazi ancestry are a carrier for Gaucher disease. Gaucher disease is also more commonly seen in the Spanish, Portuguese, Swedish, Greek, and Albanian population.

If your child has Gaucher disease, we would assume you to be an obligate carrier for Gaucher disease placing your family members at risk to be carriers for the condition. Testing is available to confirm your carrier status. Once your status has been confirmed, carrier testing can be offered to additional family members to clarify their chance of having a child with Gaucher disease.

Gaucher Patient Advocacy groups around the world are always grateful for donations to help fund research, provide patient resources and improve the lives of patients living with Gaucher disease. To begin a search for an advocacy partner in your country, type Gaucher advocacy groups in the browser.

In the United States, the National Gaucher Foundation and the Gaucher Community Alliance are valued resources for many patients living with Gaucher disease.

Patients with Gaucher disease should locate their nearest Lysosomal Storage Disease Center with physicians and genetic counselors who specialize in treating individuals with Gaucher disease. If that is not possible, patients are often seen by metabolic geneticists, metabolic specialists or hematologists.

As Gaucher disease may also affect your bones, a good orthopedics (bone doctor) may be an integral part of your team of physicians that you visit.

National Gaucher Foundation (NGF)
5410 Edson Lane
Suite 220
Rockville, Maryland 20852
Phone: 800-504-3189 (toll-free)
Email: [email protected]
http://www.gaucherdisease.org

Gaucher Community Alliance
Phone: 504-782-2057 |
Email: [email protected]
https://www.gauchercommunity.org/

The Gauchers Association Ltd
Evesham House Business Centre
48/52 Silver Street
Dursley Gloucestershire GL11 4ND
United Kingdom
Phone: +44 1453 549231
Email: [email protected]
http://www.gaucher.org.uk

Center for Jewish Genetic Disorders
Ben Gurion Way
30 South Wells Street
Chicago IL 60606
Phone: 312-357-4718
Email: [email protected]
http://www.jewishgenetics.org

There is ongoing research and clinical studies involving Gaucher disease that are open and recruiting patients. The types of studies range from investigations of new medications to novel treatment options to the study of the natural progressions of the disease. To find up-to-date applicable clinical trial information, visit www.clinicaltrials.gov and search "Gaucher disease".

Antidote also offers a handy tool to find clinical trials.

In the United States, The National Gaucher Foundation offers a comprehensive list of physicians and treatment centers for Gaucher disease in different states in the US. Please contact the National Gaucher Foundation for the complete list.

Patient advocacy groups in various countries can help you find a physician in your area, region or geographic area.

You can have the carrier testing at any time, but the best time is before you start a family. Ask your doctor or genetic counselor to give you a test if you are planning a family, or are at the start of pregnancy. Carrier testing for Gaucher disease is usually not recommended for children under 18 years of age, as being a carrier generally does not affect one’s health. Your children can decide if they want carrier testing when they become adults or reach reproductive age.

Type 2 Gaucher disease is the most severe of the three types of Gaucher disease. It involves severe neurological symptoms in newborn babies. Affected individuals have significantly shortened life span. Death usually occurs by age 2. Treatment is usually not effective with type 2 Gaucher disease.

In 2017, Gaucher disease is currently tested for in Missouri and Illinois on their newborn screening tests. It is also being testing for in some hospitals in New York. Gaucher disease is not yet on the recommended uniform screening panel (RUSP) that many states use to decide which tests to run on newborns. Newborn screening for lysosomal storage disorders, for which Gaucher disease is the most common, is a hot topic in the news. This list of states will likely increases as time goes on.

The teenage years are a time when teens often begin separating their thoughts, goals, and self-image from those of their parents. They begin exploring who they are and who they want to become as they enter adulthood. For people living with a chronic disease, like a lysosomal storage disease, the teen years should also include a gradual transfer of medical care responsibility from parents to the teens themselves. As you might guess, it’s a lot easier to learn to do this slowly and with a plan, rather than jumping headfirst into a fast and confusing crash course of medical needs on your 18th birthday. This workbook, Transitions: Managing Your Own Healthcare, is packed full of exercises designed to help teens figure out how much they already are managing their own healthcare and how to uncover what they still need to learn and master to successfully manage their own healthcare.
Transitions: Managing Your Own Healthcare

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

Chaperone-mediated enzyme enhancement therapy uses pharmacologic chaperones, which serve as a folding template for the defective enzyme. Such agents may restore enzyme activity and clear stored substrate. The drug isofagamine, which has been shown to exhibit these properties in research studies, is currently in clinical trials to establish its safety and efficacy when given to adults with type 1 Gaucher disease.

Bone marrow transplantation (BMT) has been undertaken in individuals with severe Gaucher disease, primarily those with chronic neurologic involvement (type 3 Gaucher disease). Successful BMT can correct the metabolic defect, improve blood counts, and reduce increased liver volume. In a few individuals, stabilization of neurologic and bone disease has occurred; however, the morbidity and mortality associated with BMT limit its use in individuals with type 1 and type 3 Gaucher disease. Therefore, this procedure has been largely superseded by enzyme replacement therapy.

However, in developing countries, a BMT may be an alternative and should be considered only when other treatment options are not available.

A parent of a child with Gaucher disease is assumed to be an obligate carrier for the condition making the chance of each future child born from the same couple 25% for Gaucher disease. Carrier testing is available to confirm this chance.

A pathogenetic variant (historically referred to as mutations) in the GBA gene cause Gaucher disease. The GBA gene is located on chromosome 1 on the long arm at region 2 band 1 (1q21). There are 300 different mutation that have been discovered in the GBA gene.

In the United States, there are three recombinant glucocerebrosidase enzyme preparations currently available. All are based on the human gene sequence, but are distinguished according to the cell types involved in their production: imiglucerase (Cerezyme®) generated in Chinese hamster ovary cells; velalglucerase alfa (VPRIV®) from human fibroblast-like cell line; and taliglucerase alfa (Elelyso®) from a carrot cell line. The experience with all three types of ERT appears comparable.

Not all countries have the same approved products. Check with your physician to determine which products are available in your specific country.

Gaucher disease was first described by Dr. Phillippe Gaucher in 1882. Gaucher disease is a lysosomal storage disease involving a deficiency (lacking) of the enzyme glucocerebrosidase (GBA). Due to a faulty GBA gene, this enzyme deficiency leads to buildup (storage) of certain lipids (fats) called glucocerebrosides (GL1) in the spleen, liver, bone marrow, and other parts of the body. Symptoms of the disease may include enlargement of the spleen and liver (a big belly or abdomen), anemia, thrombocytopenia (low platelet counts), bone pain, and bone fragility.

Gaucher disease is one of the most common lysosomal storage disorders affecting ~1:40,000 to 60,000. Like other lysosomal storage disorders, there is a a wide spectrum of signs and symptoms including 3 different types of the disease described as type 1, the most common type of the disorder that does not affect the central nervous system; type 2 an acute, severe type of Gaucher disease and type 3 disease that is a characterized as a chronic form that does affect the central nervous system.

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. Regular intravenous (IV) infusions of the recombinant enzymes (ERT) have been demonstrated to be safe and effective in reversing those features resulting from hematologic (blood) and visceral (liver/spleen) involvement. ERT is well tolerated. Individuals with type 1 Gaucher disease report improved health-related quality of life after 24-48 months of ERT.

Some of the other names used for Gaucher disease include:

There is sometimes overlap between enzyme results for patients with Gaucher disease and patients without the disease. In this case, it can be difficult to correctly interpret the test result. Genetic testing may be recommended for these patients to clarify their result.

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

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. 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).

In type 3 Gaucher disease, symptoms usually develop in childhood. They have all the symptoms of type 1 Gaucher disease; however, they also have neurological symptoms like seizures, ataxia (moving funny), and abnormal eye movements. 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. Affected individuals can live into the 3rd or 4th decades of their lives.

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 nucleus. This material also stains positively with periodic acid-Schiff (PAS) reagent.

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

Different genetic mutations may lead to difference in severity and presentation of Gaucher disease, though the correlation is often imperfect. At present the exact genetic factors that influence disease severity or progression are not known.

In general, affected individuals who have two copies of a mutation called N370S tend to have milder disease than those who have one copy of the N370S mutation and another mutation- but remember, this is a general rule of thumb and not an absolute. Individuals with at least one copy of the N370S mutation have type 1 Gaucher disease. Individuals who have two copies of a mutation called L444P tend to have severe disease, often with neurologic complications (i.e., types 2 and 3 Gaucher disease).

Analgesics for bone pain
Joint replacement surgery for relief from chronic pain and restoration of function
Bisphosphanates (e.g. Boniva) and calcium for osteoporosis
Prophylactic antibiotics
Blood transfusions

On the genetic testing registry, there are 86 tests available for GBA gene in a total of 41 commercial labs in the US. The list of laboratories for genetic testing can be found at:
[link url="” target=”_blank”>http://www.ncbi.nlm.nih.gov/gtr/tests/?term=Gaucher disease

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

Patients on enzyme replacement therapy (ERT) are usually dependent on this treatment for life. Some individuals can have infusion-related reactions to ERT, but these are typically mild and do not occur that frequently. ERT also involves Intravenous (IV) administration, which the patient may have to receive from a treatment center and requires administration by a nurse. ERT is also very costly. However, home therapy is an available option in many countries. Talk to your doctor to determine if this is an option for you.

Gaucher disease is classified into three types. Type 1 is the most common form of Gaucher disease, representing about 95% of Gaucher disease patients. It is the non-neuronopathic form of the condition. Type 2 Gaucher disease is the acute, neuronopathic form and is the most severe type. Type 3 Gaucher disease is the chronic, neuronopathic form of Gaucher disease. Neuronopathic is a term physicians use that describes ‘affecting the brain’. When a patient is diagnosed with Gaucher disease, your doctor can tell by your genotype (the genes you inherit from your parents), if you have type 1 Gaucher disease by the presence of a certain variant (N370S). While there’s very few absolutes in medicine, in the United States, this particular N370S variant pretty much determines that you have type 1 Gaucher disease.

The targeted mutation test can identify about 89% of carriers with Gaucher disease. The sequencing method can identify over 99% of carriers with Gaucher disease.

The following tests are used to monitor the effectiveness of Gaucher disease therapy:

Carriers of Gaucher disease are healthy and require no medical treatment. The fact that an individual is a carrier only becomes important if their partner is also a carrier and they have a pregnancy together. In that case, there is a chance (up to 25%, or 1 in 4) that the baby may be born with Gaucher disease.

Gaucher disease is unique. Unlike most autosomal recessive genetic diseases, carriers for Gaucher disease are at increased risk for Parkinson disease.

Gene therapy involves the introduction of GBA into hematopoietic stem cells. There is quite an interest in gene therapy for the treatment of lysosomal storage disorders. Clinical Trials. gov (www.clinicaltrials.gov) provides the most up-to-date information on clinical trials in this exciting field.

Gaucher disease has several FDA approved treatments. The main treatment used in Gaucher disease is enzyme replacement therapy (ERT) which is given to replace the missing enzyme in Gaucher disease. In the United States, there are 3 approved enzyme replacement therapies available. Substrate reduction therapy (SRT) is also an FDA approved therapy option. Unfortunately, no therapy is 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.

Due to the different approval processes around the globe, not all products may be available in your country.

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 population.

GBA mutations have been identified in 5%-10% of individuals with Parkinson disease. 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.

Substrate reduction therapy (SRT) works by reducing the amount of fat (GL1 substrate) made by the body that will eventually be turned into waste products. The goal is to limit the fat buildup (GL1 substrates) to a level that can be effectively cleared by the naturally occurring enzyme (all living people with Gaucher disease have a little enzyme) with residual activity. As SRT is a small molecule, the benefit is an oral medication.

Miglustat is recommended as a treatment alternative for those with hypersensitivity to ERT or poor venous access (problems with multiple need sticks).
Ceredelga is a first-line therapy for the treatment of adult patients with Gaucher disease.

Currently, there is no cure for Gaucher disease, but there are treatments and medications available to manage symptoms. Gene therapy trials are underway with the promise for the future.

In the United States, The National Gaucher Foundation Inc., a ThinkGenetic Advocacy Partner, and the Gaucher Community Alliance offer several different ways to connect with others living with Gaucher disease. There are programs like the Gaucher mentor program, an online Gaucher chat support, and Gaucher patient registry that can help individuals with Gaucher disease to connect with one another.

Visit these groups to find resources nearest to you.

Many countries around the globe provide a patient organization to help meet your needs. In the browser, type in Gaucher advocacy to find a program.

It has been estimated that about 1 in 200 people in the general United States population is a carrier for Gaucher disease. The carrier rate is much high in other populations including people of Ashkenazi Jewish heritage in which 1 in 18 individuals are carriers of Gaucher disease.

Enzyme testing is not reliable for carrier testing 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. There are two common methods for carrier testing. One test is called the targeted mutation test, which looks for the 4 common GBA mutations seen the in Ashkenazi Jewish population. This test is often used for individuals of Ashkenazi Jewish background. The second test is called sequencing and looks for all the DNA bases in the GBA gene.

Gaucher disease is inherited in an autosomal recessive fashion, which means both parents must be carriers for Gaucher disease for there to be a chance of having a child with that disease. A carrier is a person who has one working copy of the gene and one copy of the gene that does not work normally. Carriers typically do not show symptoms of the disease or have medical problems associated with being a carrier.

The enzyme test to determine the level of glucocerebrosidase 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.

There are several tests that are conducted to confirm a suspected case of Gaucher disease, including an enzyme test to determine the level of glucocerebrosidase. A genetic test, also known as a DNA test can be performed to check for the underlying genetic defect causing Gaucher disease.

Gaucher disease has an incidence of about 1/40,000 to 1/100,000, which includes all three types of Gaucher disease. It affects males and females equally. Type 1 Gaucher disease is estimated to affect ~1: 40,000 to 1:60,000 individuals. Patients of Ashkenazi ancestry have an increased incidence of type 1 Gaucher disease. It might surprise you to learn that type 1 Gaucher disease, not Tay-Sachs, is the most common Jewish genetic disease and ~1:15-18 are carriers for the disease.

Pregnancy may affect the course of Gaucher disease both by exacerbating preexisting symptoms and by triggering new features such as bone pain. Women with severe thrombocytopenia and/or clotting abnormalities may have an increased risk of bleeding around the time of delivery. Talk to your physician prior to getting pregnant and how to best manage your pregnancy if you are pregnant.

Prenatal diagnosis for pregnancies at increased risk is possible if the mutation in GBA gene in the family is known. Testing in the pregnancy can be done by invasive procedures, such as chorionic villi sampling or amniocentesis.

Requests for prenatal testing for treatable conditions such a Gaucher disease type 1 are not common. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in individuals with moderate to severe thrombocytopenia.

The main signs and symptoms of Gaucher disease are: