What is Gaucher disease?
Gaucher disease is characterized as a lysosomal storage disorder [1]. Individuals affected by the disease have a deficiency of glucocerebrosidase (GCase), an enzyme that is essential to breaking down lipids, or fats, within the cells. In turn, sphingolipids, a type of fatty substance, accumulate in the spleen, liver, and in the bone marrow, leading to symptoms of Gaucher disease [2].
|
Figure 1. The structure of the glucocerebrosidase enzyme
|
How is Gaucher disease diagnosed?To diagnose Gaucher disease, a healthcare provider will take into account a patient's family medical history, symptoms, and results from a blood test [4]. Doctors typically order the beta-glucosidase leukocyte (BGL) test to analyze an individual's levels of glucocerebrosidase [5, 6].
|
What causes Gaucher disease?
What are the different types of Gaucher disease?
There are different GBA1 mutations that are linked to three different types of Gaucher disease, which range in terms of severity [9].
Type 1In the United States, the most prevalent form of Gaucher disease is type 1. Symptom onset can occur during childhood or adulthood. Although there is not a cure for Gaucher disease, treatment options exist for type 1 [2]. |
Type 2Individuals with type 2 Gaucher disease experience symptoms by the time they reach 6 months of age. Treatment options are not available for this form of the disease, which is fatal by age two or three [2]. |
Type 3Type 3 is the most prevalent form of Gaucher disease globally. Individuals typically begin to experience symptoms by age 10. With treatment, they can live for several decades [2]. |
Are there other features that distinguish the three types of Gaucher disease?
Individuals with type 2 and type 3 Gaucher disease may experience neurological symptoms [2]. To learn more about the different symptoms of the three types of Gaucher disease, please watch from 2:09-3:51 of the video linked here.
Are there treatments for Gaucher disease?
There are two treatment options for patients with Type 1 Gaucher disease:
- Enzyme Replacement Therapy (ERT): Every two weeks, patients receive an intravenous infusion which provides them with a modified form of GCase to counteract their deficiency [2, 5].
- Substrate Reduction Therapy (SRT): Patients receive medicine orally on a regular basis to lower the levels of fatty chemicals in order to prevent them from accumulating in their cells [2, 5].
Unfortunately, the neurological symptoms associated with Gaucher disease are not receptive to treatment [2]. The enzyme used in ERT struggles to cross the blood-brain barrier [10].
Who is at risk for Gaucher disease?
Individuals of Ashkenazi Jewish background (from Eastern Europe) are at greater risk for type 1 Gaucher disease [2]. Approzimately 10% of Ashkenazi Jews are carriers for the mutation that causes Gaucher disease and 1/450 Ashkenazi Jews have the disorder [2].
What is the current status of Gaucher disease research?
|
Prevail is working on a treatment referred to as Pr001. The goal is to use AAV9, a viral vector, to send a healthy copy of GBA1 into a patient's cells [12].
|
What is the gap in knowledge?
Microglia serve as a type of immune cell in the brain [13]. In the most severe cases of Gaucher disease, individuals affected experience neurological symptoms. Research shows that these individuals often have increased activation of their microglia, which may induce neuroinflammation [14]. GBA1 regulates microglial cell proliferation, lipid storage, and lysosomal function [15]. Despite extensive research on Gaucher disease, the role of GBA1 in the regulation of lysosome function in microglial cells in the brain remains unclear.
In order to understand Gaucher disease, what are some of the key takeaways?
For a summary of the information found on this home page, please watch the following video.
(American Society of Gene + Cell Therapy, 2021)
Are there resources available to support individuals affected by Gaucher disease?
Website Visits
Citations
1. National Gaucher Foundation. (2023, February 10). Lysosomal Storage Disease & Disorder. gaucherdisease.org. Retrieved February 21, 2023, from https://www.gaucherdisease.org/about-gaucher-disease/what-is/lysosomal-storage-disorders/
2. Cleveland Clinic. (2020, September 14). Gaucher disease: Causes, symptoms & treatment. my.clevelandclinic.org. Retrieved February 21, 2023, from https://my.clevelandclinic.org/health/diseases/16234-gaucher-disease#:~:text=Healthcare%20providers%20diagnose%20Gaucher%20disease,the%20disease%20to%20their%20children
3. National Gaucher Foundation. (2022, April 27). Gaucher disease symptoms. gaucherdisease.org. Retrieved February 21, 2023, from https://www.gaucherdisease.org/about-gaucher-disease/symptoms/
4. National Gaucher Foundation. (2022, April 27). Testing for Gaucher Disease. gaucherdisease.org. Retrieved February 21, 2023, from https://www.gaucherdisease.org/gaucher-diagnosis-treatment/testing/
5. National Gaucher Foundation. (2022, April 6). Gaucher Disease Diagnosis & Treatment. gaucherdisease.org. Retrieved February 21, 2023, from https://www.gaucherdisease.org/gaucher-diagnosis-treatment/
6. Gaucher Disease News. (2020, May 4). BGL Test. gaucherdiseasenews.com. Retrieved February 21, 2023, from https://gaucherdiseasenews.com/bgl-test/. (2019, November 19). Gaucher Disease.
7. Gaucher Disease | Johns Hopkins Medicine. Retrieved February 21, 2023, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/gaucher-disease#:~:text=It%20is%20caused%20by%20a,their%20child%20to%20get%20Gaucher
8. National Library of Medicine. (n.d.). Gba1 glucosylceramidase beta 1 [homo sapiens (human)]. National Center for Biotechnology Information. Retrieved April 14, 2023, from https://www.ncbi.nlm.nih.gov/gene/2629
9. Pastores GM, Hughes DA. Gaucher Disease. 2000 Jul 27 [Updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1269/
10. Gaucher Basics. Childrens Gaucher Research Fund. (n.d.). Retrieved April 22, 2023, from https://www.childrensgaucher.org/about-gaucher/gaucher-basics/
11. National Gaucher Foundation. (2022, March 24). Gene therapy for Gaucher Disease: AAV, Lentivirus, & More. gaucherdisease.org. Retrieved February 23, 2023, from https://www.gaucherdisease.org/blog/gene-therapy-for-gaucher-disease-aav-lentivirus-more/
12. Our Programs - our pipeline. Prevail. (2023, January 13). Retrieved February 23, 2023, from https://www.prevailtherapeutics.com/programs/
13. Ozturk, M. M., & Wu, W. (2022, March 15). Microglia: The protectors of the brain. Science in the News. Retrieved March 9, 2023, from https://sitn.hms.harvard.edu/flash/2022/microglia-the-protectors-of-the-brain/
14. Feldman, R. A. (2022, August 22). Gaucher Disease: Microglia orchestrate neuroinflammation. eLife. Retrieved March 28, 2023, from https://elifesciences.org/articles/81890
15. Consortium, G. O. (n.d.). Lysosomal acid glucosylceramidase. AmiGO 2: Gene Product Details for UniProtKB:P04062. Retrieved March 5, 2023, from http://amigo.geneontology.org/amigo/gene_product/UniProtKB:P04062
2. Cleveland Clinic. (2020, September 14). Gaucher disease: Causes, symptoms & treatment. my.clevelandclinic.org. Retrieved February 21, 2023, from https://my.clevelandclinic.org/health/diseases/16234-gaucher-disease#:~:text=Healthcare%20providers%20diagnose%20Gaucher%20disease,the%20disease%20to%20their%20children
3. National Gaucher Foundation. (2022, April 27). Gaucher disease symptoms. gaucherdisease.org. Retrieved February 21, 2023, from https://www.gaucherdisease.org/about-gaucher-disease/symptoms/
4. National Gaucher Foundation. (2022, April 27). Testing for Gaucher Disease. gaucherdisease.org. Retrieved February 21, 2023, from https://www.gaucherdisease.org/gaucher-diagnosis-treatment/testing/
5. National Gaucher Foundation. (2022, April 6). Gaucher Disease Diagnosis & Treatment. gaucherdisease.org. Retrieved February 21, 2023, from https://www.gaucherdisease.org/gaucher-diagnosis-treatment/
6. Gaucher Disease News. (2020, May 4). BGL Test. gaucherdiseasenews.com. Retrieved February 21, 2023, from https://gaucherdiseasenews.com/bgl-test/. (2019, November 19). Gaucher Disease.
7. Gaucher Disease | Johns Hopkins Medicine. Retrieved February 21, 2023, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/gaucher-disease#:~:text=It%20is%20caused%20by%20a,their%20child%20to%20get%20Gaucher
8. National Library of Medicine. (n.d.). Gba1 glucosylceramidase beta 1 [homo sapiens (human)]. National Center for Biotechnology Information. Retrieved April 14, 2023, from https://www.ncbi.nlm.nih.gov/gene/2629
9. Pastores GM, Hughes DA. Gaucher Disease. 2000 Jul 27 [Updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1269/
10. Gaucher Basics. Childrens Gaucher Research Fund. (n.d.). Retrieved April 22, 2023, from https://www.childrensgaucher.org/about-gaucher/gaucher-basics/
11. National Gaucher Foundation. (2022, March 24). Gene therapy for Gaucher Disease: AAV, Lentivirus, & More. gaucherdisease.org. Retrieved February 23, 2023, from https://www.gaucherdisease.org/blog/gene-therapy-for-gaucher-disease-aav-lentivirus-more/
12. Our Programs - our pipeline. Prevail. (2023, January 13). Retrieved February 23, 2023, from https://www.prevailtherapeutics.com/programs/
13. Ozturk, M. M., & Wu, W. (2022, March 15). Microglia: The protectors of the brain. Science in the News. Retrieved March 9, 2023, from https://sitn.hms.harvard.edu/flash/2022/microglia-the-protectors-of-the-brain/
14. Feldman, R. A. (2022, August 22). Gaucher Disease: Microglia orchestrate neuroinflammation. eLife. Retrieved March 28, 2023, from https://elifesciences.org/articles/81890
15. Consortium, G. O. (n.d.). Lysosomal acid glucosylceramidase. AmiGO 2: Gene Product Details for UniProtKB:P04062. Retrieved March 5, 2023, from http://amigo.geneontology.org/amigo/gene_product/UniProtKB:P04062
Links to Images
1. Cover Image: https://www.newscientist.com/article/2358095-genes-for-gaucher-disease-may-have-protected-jewish-people-against-tb/
2. Image of Gaucher disease symptoms: https://www.mountsinai.org/health-library/diseases-conditions/gaucher-disease
3. Image for Gaucher disease diagnosis: https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/blood-test
4. Autosomal recessive inheritance: https://gaucher-institute.com/burden-of-disease/genetic-inheritance-of-gaucher-disease
5. Gaucher disease research: https://www.prevailtherapeutics.com/programs/
6. Connect with others image: https://www.gaucherdisease.org/about-gaucher-disease/resources/connect/ (and the image underlaying it: https://www.engadget.com/2017-02-20-dna-computers-could-lead-to-self-activated-smart-pills.html)
2. Image of Gaucher disease symptoms: https://www.mountsinai.org/health-library/diseases-conditions/gaucher-disease
3. Image for Gaucher disease diagnosis: https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/blood-test
4. Autosomal recessive inheritance: https://gaucher-institute.com/burden-of-disease/genetic-inheritance-of-gaucher-disease
5. Gaucher disease research: https://www.prevailtherapeutics.com/programs/
6. Connect with others image: https://www.gaucherdisease.org/about-gaucher-disease/resources/connect/ (and the image underlaying it: https://www.engadget.com/2017-02-20-dna-computers-could-lead-to-self-activated-smart-pills.html)
This website was created by Jenna Gold for her capstone project in Genetics 564 at UW-Madison. This website was last updated on 5/12/2023.