Gaucher Disease
What is Gaucher Disease?
Gaucher’s Disease (GD) is a rare genetic disorder that affects how the body breaks down and stores certain types of fats (lipids), leading to an accumulation in various organs. It is part of a group of disorders called lysosomal storage diseases. GD is caused by mutations in the GBA gene, which provides instructions for making an enzyme called glucocerebrosidase (also known as glucosylceramidase). Glucocerebrosidase breaks down a fatty substance called glucocerebroside. When this enzyme is deficient or malfunctioning, glucocerebroside accumulates, particularly in the liver, spleen, and bone marrow. GD is classified into three main types based on the severity and symptoms. Type 1 (Non-neuronopathic) is the most common form, affecting primarily the liver, spleen, and bones. There is little to no involvement of the brain. Type 2 (Acute Neuronopathic) is a severe form that affects the brain, leading to neurological symptoms such as seizures and severe developmental delays. This type usually appears in infancy and is often fatal within the first few years of life. Type 3 (Chronic Neuronopathic) is similar to Type 2, but with a slower progression of neurological symptoms. This type can appear in childhood and may progress into adulthood, affecting the brain as well as other organs. The rarest form of GD is Fetal GD where death occurs in utero or right after birth.
Synonyms
- Gaucher splenomegaly
- Gaucher syndrome
- Acid beta-glucosidase deficiency
- Acute cerebral Gaucher disease
- Cerebroside lipidosis syndrome
- Glucocerebrosidase deficiency
- Glucocerebrosidosis
- Glucosyl cerebroside lipidosis
- Glucosylceramidase deficiency
- Glucosylceramide beta-glucosidase deficiency
- Kerasin histiocytosis
- Kerasin lipoidosis
- Kerasin thesaurismosis
- Lipoid histiocytosis (kerasin type)
- Sphingolipidosis 1
Gaucher’s Disease (GD) is a rare genetic disorder that affects how the body breaks down and stores certain types of fats (lipids), leading to an accumulation in various organs. It is part of a group of disorders called lysosomal storage diseases. GD is caused by mutations in the GBA gene, which provides instructions for making an enzyme called glucocerebrosidase (also known as glucosylceramidase). Glucocerebrosidase breaks down a fatty substance called glucocerebroside. When this enzyme is deficient or malfunctioning, glucocerebroside accumulates, particularly in the liver, spleen, and bone marrow. GD is classified into three main types based on the severity and symptoms. Type 1 (Non-neuronopathic) is the most common form, affecting primarily the liver, spleen, and bones. There is little to no involvement of the brain. Type 2 (Acute Neuronopathic) is a severe form that affects the brain, leading to neurological symptoms such as seizures and severe developmental delays. This type usually appears in infancy and is often fatal within the first few years of life. Type 3 (Chronic Neuronopathic) is similar to Type 2, but with a slower progression of neurological symptoms. This type can appear in childhood and may progress into adulthood, affecting the brain as well as other organs. The rarest form of GD is Fetal GD where death occurs in utero or right after birth.
GD has an overall estimated worldwide prevalence of 1-9 in 100,000.
GD has an overall estimated incidence of 1 in 60,000.
The incidence in Ashkenazi Jews can be as high as 1 in 600.
| Name | Abbreviation |
|---|---|
| Gaucher splenomegaly | |
| Gaucher syndrome | |
| Acid beta-glucosidase deficiency | |
| Acute cerebral Gaucher disease | |
| Cerebroside lipidosis syndrome | |
| Glucocerebrosidase deficiency | |
| Glucocerebrosidosis | |
| Glucosyl cerebroside lipidosis | |
| Glucosylceramidase deficiency | |
| Glucosylceramide beta-glucosidase deficiency | |
| Kerasin histiocytosis | |
| Kerasin lipoidosis | |
| Kerasin thesaurismosis | |
| Lipoid histiocytosis (kerasin type) | |
| Sphingolipidosis 1 |
GD is caused by mutations in the GBA gene coding for glucocerebrosidase enzyme responsible for breaking down glucocerebroside. Enzyme activity reduced to 15% of normal or lower is diagnostic of GD with even the most severe cases retaining some level of enzyme function. This disorder is inherited in an autosomal recessive pattern, meaning you need to inherit a mutated copy from both parents (see RareShare Guide on Genetic Inheritance). The accumulation of glucocerebroside in macrophages (a type of white blood cell) results in transformation into characteristic Gaucher cells. Gaucher cells most commonly invade the bone marrow, liver, and spleen, where they displace the local cell populations. This results in many of the symptoms associated with GD. The severity of glucocerebrosidase disruption determines the type of GD. Milder glucocerebrosidase disruption leads to development of type 1 GD. Type 1 GD is chronic and has no neurological dysfunction. Greater degree of glucocerebrosidase disruption leads to development of type 2 and type 3 which have neurological involvement. Type 2 GD, associated with the lowest levels of glucocerebrosidase activity, has severe early onset neurological dysfunction resulting in death by age 2. Type 3 GD is the subacute neurological version which involves progressive neurological symptoms beginning in childhood combined with the visceral organ (liver, spleen, bone marrow) effects seen in type 1.
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Enlarged liver and spleen (hepatosplenomegaly)
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Abdominal pain
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Low blood, platelet counts (anemia, thrombocytopenia)
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Bone pain and fractures
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Growth delays in children
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Delayed puberty
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Fatigue
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Easy bruising and bleeding
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Interstitial Lung disease
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Yellow-brown hyperpigmentation
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Protein, blood in the urine (rarely)
Neurological symptoms (Types 2 and 3): -
Seizures
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Cognitive impairment
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Eye movement abnormalities
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Developmental delays
| 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 |
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Blood tests: low glucocerebrosidase enzyme activity, anemia, thrombocytopenia
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Genetic testing: confirm GBA gene mutation
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Imaging: bone density scans showing decreased density, ultrasound showing organ enlargement
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Newborn screening: currently offered in Missouri, New York, and Illinois
Diagnostic testing includes 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.
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Enzyme Replacement Therapy (ERT): Intravenous infusions of recombinant glucocerebrosidase; ineffective for neurological involvement in types 2,3
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Substrate Reduction Therapy (SRT): Oral medications to reduce glucocerebroside production; ineffective for neurological involvement in types 2,3
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Blood transfusions for anemia
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Pain management for bone symptoms
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Surgery for severely enlarged spleen
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Liver transplantation for severe liver disease
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Monitor coagulation labs prior to surgical/dental/obstetric procedures
The outlook for Gaucher’s disease depends on the type considered. Recent advancements in enzyme replacement therapy have made it possible to live nearly full lives with type 1 GD as long as treatment is initiated early. Early treatment is vital in preventing irreversible complications like bone necrosis and multiple myeloma. Type 2 has a poor prognosis as neurological damage is rapid and severe, often resulting in early childhood death. Fetal GD has a poor prognosis as well, with death occurring in utero or at birth. Type 3 GD has a variable prognosis depending on severity and progression of neurological symptoms. Currently, there is no treatment for the neurological symptoms of GD. Further, patients with neurological involvement are at increased risk of developing Parkisnon’s Disease and Lewy Body Dementia. Research is being conducted to better understand and address GD, especially in the area of gene therapy. Individuals should receive genetic counseling due to the chance of transmitting the disease to children as well as possible difficulty navigating the transition from pediatric to adult healthcare.
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.
Homepage | Know Gaucher Disease. (2023). Knowgaucherdisease.com. https://www.knowgaucherdisease.com/hcp/home
Stirnemann, J., Belmatoug, N., Camou, F., Serratrice, C., Froissart, R., Caillaud, C., Levade, T., Astudillo, L., Serratrice, J., Brassier, A., Rose, C., Billette de Villemeur, T., & Berger, M. G. (2017). A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. International Journal of Molecular Sciences, 18(2), 441. https://doi.org/10.3390/ijms18020441
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 |
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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...
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Cerezyme shortage
Created by tony123 | Last updated 17 Aug 2009, 05:49 PM
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