Gaucher Disease
What is Gaucher Disease?
Gaucher disease is an inherited metabolic disease that is caused by a deficiency of the enzyme, beta-glucocerebrosidase, which, in turn, results in an accumulation of the fat, glucosylceramide in many tissues. As a result, the nucleus of the cell is pushed to the side and the excess lipid occupies most of the space in the cell. Such lipid-laden cells are often called "Gaucher cells". There are three commonly recognized types of Gaucher disease:
Type 1 Gaucher disease is the most common form and historically has been described as not affecting the central nervous system (brain and spinal cord).
Gaucher disease types 2 and 3 are characterized by their effect on the central nervous system. A major difference between type 2 and type 3 is that in type 3, the affected individual starts to develop the symptoms later in childhood, whereas in type 2 the onset of symptoms is before the age of 2.
Gaucher disease is an inherited metabolic disease that is caused by a deficiency of the enzyme, beta-glucocerebrosidase, which, in turn, results in an accumulation of the fat, glucosylceramide in many tissues. As a result, the nucleus of the cell is pushed to the side and the excess lipid occupies most of the space in the cell. Such lipid-laden cells are often called "Gaucher cells". There are three commonly recognized types of Gaucher disease:
Type 1 Gaucher disease is the most common form and historically has been described as not affecting the central nervous system (brain and spinal cord).
Gaucher disease types 2 and 3 are characterized by their effect on the central nervous system. A major difference between type 2 and type 3 is that in type 3, the affected individual starts to develop the symptoms later in childhood, whereas in type 2 the onset of symptoms is before the age of 2.
In the general population, Gaucher disease occurs in approximately 1 in 50,000 - 100,000 people. Type 1 is the most common form (occurs in 90% of cases) and occurs more frequently in people of Ashkenazi Jewish heritage than in those of other ethnicities. Amongst the Ashkenazi Jewish population, the condition affects 1 in 500 - 1,000 individuals. The other forms of Gaucher are uncommon in comparison and do not occur more frequently in people of Ashkenazi Jewish descent.
Gaucher disease type 1 is caused by mutations in a gene called the GBA gene. The GBA gene codes for a lysosomal enzyme called glucocerebrosidase. Glucocerbrosidase is an enzyme that is responsible for breaking down a fatty substance, glucocerebroside, into glucose (a sugar) and a simpler fat called ceramide. Mutated GBA genes reduce the activity of glucocerebrosidase enzyme significantly, which causes a toxic accumulation of glucocerebroside within cells. On rare occasions, a mutation in a gene called the PSAP gene, which codes for saposin, a protein required for activation of beta-glucocerebrosidase, may cause Gaucher disease.
Gaucher disease is inherited in an autosomal recessive mode, meaning that both parents need to carry the gene for the disorder, and they both must pass this gene to their offspring for him/her to be affected.
Type 1 Gaucher disease is known as non-neuronopathic Gaucher disease as the central nervous system was historically considered to be unaffected. The symptoms of type I Gaucher disease range from mild to severe and can appear anytime from childhood to adulthood. Characteristic features are enlargement of the liver and spleen, low number of red blood cells, easy bruising caused by low platelet counts, Lung disease, and bone abnormalities such as pain, fractures. Patients may have arthritis type pain, often involving the hips and knees.
Types 2 and 3 Gaucher disease are considered neuronopathic forms as they are characterized by their effects on the central nervous system. In addition to the symptoms of Type 1, individuals with these forms will exhibit neurological degradation.
Individuals with type 2, the acute form, exhibit, sudden body movements that are involuntary and irregular, an abnormal increase in muscle tension (hypertonia), mental disability, and breathing pauses especially during sleep (apnea). In Type 3, the subacute form, the symptoms include muscle twitches known as myoclonus, convulsions, dementia and lack of control of voluntary eye movement.
| Name | Description |
|---|---|
| Buildup of fatty material | Fatty material can collect in the spleen, liver, kidneys, lungs, brain and bone marrow |
| Hypersplenism | Increased destruction of red and white blood cells and platelets |
| Osteoporosis | Osteoporosis |
For individuals who bruise easily and have anemia without a clear reason, a diagnostic test for Gaucher disease should be considered. If the individual has an enlarged liver or spleen and fractures, Gaucher disease becomes a more likely possibility.
Diagnostic testing that confirms a diagnosis of Gaucher disease type I include measuring the level of glucocerebrosidase in blood (white blood cells) and performing mutation analysis of the GBA gene.
It is possible to diagnose Gaucher disease prenatally through amniocentesis or chorionic villus sampling (CVS). In amniocentesis, the test is performed by analyzing a sample of the fluid in which the fetus grows. In contrast, in CVS the sample is removed from the placenta.
Treatments for Gaucher disease type I include intravenous enzyme replacement therapy (ERT) that provides glucocerebrosidase enzyme to the patient through an intravenous infusion, and substrate reducing therapy (SRT). ERT has demonstrated the ability to decrease liver and spleen size, improve platelet count and hemogloblin, and improve bone health. Enzyme replacement medications currently available for Gaucher disease are Imiglucerase (Cerezyme), Taliglucerase alfa (Elelyso), and Velaglucerase alfa (VPRIV). ERT does not have appreciable ability to reduce central nervous system effects of Gaucher disease types 2 and 3. For Types 2 and 3, there are currently no medications available to reverse the damage done to the brain; however, there are some new in that are being researched and developed currently but not yet in the market. SRT therapies are medications taken by mouth that inhibit glucosylceramide synthase in the glycosphingolipid metabolic pathway and thereby inhibit production of glucocerebrosie. Miglustat (Zavesca) and Eliglustat (Cerdelga) are examples of this types of medication. SRT therapies are approved for treatment of Gaucher disease type I.
For individuals with Gaucher disease type 1, treatment usually results in significant improvement in symptom management. Unfortunately, effective treatments for type 2 and type 3 disease have not been identified yet. The prognosis for Gaucher disease type II is poor and it usually leads to death before the age of 2. Patients with Gaucher disease type 3 may live into young adulthood.
Gaucher disease can present a wide variety of physical, emotional, and social difficulties to both the individual, their family, and their friends.
A major challenge for people with Gaucher disease as well as those who carry the gene revolve around having children. A genetic counselor can help answer such questions about the risk persons who have Gaucher disease or are carriers of a GBA mutation have children who are affected with Gaucher disease.
In terms of managing pain, utilizing pain-relieving techniques can help to reduce the pain due to movement. Lifestyle changes can also be made so as to limit the pain.
Due to anemia and enlargement of the liver and spleen, fatigue often appears in individuals with Gaucher disease. The best way of reducing this challenge is to pace daily activities, refraining from intensive activities within a short period of time
Genetics Home Reference. Gaucher disease. http://ghr.nlm.nih.gov/condition/gaucher-disease. Updated September 2014, Accessed March 1, 2016.
Genetic and Rare Diseases Information Center. Gaucher disease. https://rarediseases.info.nih.gov/gard/8233/gaucher-disease/resources/3. Updated Novemeber 4, 2015. Accessed March 1, 2016.
Hmosh, A. Gaucher disease, type I. OMIM. http://www.omim.org/entry/230800?search=gaucher%20disease&highlight=gaucher%20disease. Updated October 3, 2010. Accessed March 1, 2016.
National Organization For Rare Disorders. Gaucher Disease. https://rarediseases.org/rare-diseases/gaucher-disease/. Updated 2014. Accessed March 1, 2016.
Belmatoug, N. Stirnemann, J. Gaucher disease. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=355. Updated February 2011. Accessed March 1, 2016.
Wikipedia. Gaucher disease. https://en.wikipedia.org/wiki/Gaucher%27s_disease. February 15, 2016. Accessed March 1, 2016.
Gaucher Care. Gaucher disease. Coping With Gaucher Disease. https://www.gauchercare.com/en/patient/living/CopingWithGaucher.aspx. Accessed March 1, 2016.
Sidransky, E. Gaucher disease. Medscape. http://emedicine.medscape.com/article/944157-workup#c3. Updated November 24, 2014. Accessed March 1, 2016.
WebMD. Gaucher’s disease. http://www.webmd.com/a-to-z-guides/gauchers-disease-symptoms-causes-treatments?page=2. Accesses March 1, 2016.
MayoClinic. Gaucher’s disease. http://www.mayoclinic.org/diseases-conditions/gauchers-disease/basics/tests-diagnosis/con-20031396. Updated June 2, 2015. Accessed March 1, 2016.
Last updated 17 Aug 2009, 05:49 PM
17 Aug 2009, 05:49 PM
Curious how everyone is planning on dealing with the Cerezyme shortage? Has anyone looked at going onto the other drugs by Shire or Protalix which are still in development?
| Title | Date | Link |
|---|---|---|
| Rare Disease Day: Parents share arduous experience, hopeful future in raising children with rare diseases | 03/05/2022 | |
| Rare genetic disease may protect Ashkenazi Jews against TB | 02/12/2023 | |
| How Common Is Gaucher Disease? | 11/11/2023 | |
| Improving the recipe for gene therapy: New treatment for Gaucher disease shows promise | 10/18/2024 |
Clinical Trials
CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access.
Enrolling is easy.
- Complete the screening form.
- Review the informed consent.
- Answer the permission and data sharing questions.
After these steps, the enrollment process is complete. All other questions are voluntary. However, these questions are important to patients and their families to create awareness as well as to researchers to study rare diseases. This is why we ask our participants to update their information annually or anytime changes to their information occur.
Researchers can contact CoRDS to determine if the registry contains participants with the rare disease they are researching. If the researcher determines there is a sufficient number of participants or data on the rare disease of interest within the registry, the researcher can apply for access. Upon approval from the CoRDS Scientific Advisory Board, CoRDS staff will reach out to participants on behalf of the researcher. It is then up to the participant to determine if they would like to join the study.
Visit sanfordresearch.org/CoRDS to enroll.
Community Leaders
Expert Questions
Ask a question
Community User List
I was diagnosed with Porphyria when i was 38 tears old
My 15 year-old daughter (July 16, 1996) was diagnosed on April 5, 2012 with Gaucher Disease Type 1.
She went from a typical child with little to no health problems to...
Start a Community
Don't See Your Condition On Rareshare?
Start your own! With a worldwide network of 8,000 users, you won't be the only member of your community for long.
FAQ
Have questions about rareshare?
Visit our Frequently Asked Questions page to find the answers to some of the most commonly asked questions.
Discussion Forum
Cerezyme shortage
Created by tony123 | Last updated 17 Aug 2009, 05:49 PM
Our Communities
Join Rareshare to meet other people that have been touched by rare diseases. Learn, engage, and grow with our communities.
FIND YOUR COMMUNITY
Our Resources
Our rare disease resources include e-books and podcasts
Our Community Leaders
Community leaders are active users that have been touched by the rare disease that they are a part of. Not only are they there to help facilitate conversations and provide new information that is relevant for the group, but they are there for you and to let you know you have a support system on Rareshare.