Rare Disease Highlight: Gaucher Disease

By Isaiah Manoogian

Gaucher Disease (GD) is a rare disease caused by GBA1 gene mutations. The GBA1 gene encodes for the production of the glucocerebrosidase (GCase) enzyme, which is in the lysosome to digest large materials.¹ Due to mutations disrupting specific pathways in the body, macrophages are transformed into Gaucher cells. The Gaucher cells infiltrate the bone marrow, spleen, liver, and potentially other organs, causing the disease’s main symptoms observed in the three primary types of GD.²  Type 1 GD (GD1) is the most common form, with signs and symptoms including, anemia and fatigue, decreased bone density, painful bone crises, and an enlarged liver and spleen. Type 2 GD (GD2) is characterized by GCase accumulating in the brain resulting in severe early life neurological symptoms, such as trouble swallowing. Trouble swallowing leads to significant breathing and feeding difficulties, and even death within the first few years of life. Type 3 GD (GD3) is similar to GD2, but the symptoms develop more gradual; seizures can be a large problem for those suffering GD3. The signs and symptoms of GD2 and GD3 also include those associated with GD1.³  Interestingly, the literature reports GBA gene mutations are the most common genetic risk factor for Parkinson’s Disease (PD), establishing a strong association between the two.⁴

After the onset of the first clinical and laboratory signs, GD is typically diagnosed years later using a specific blood test. If GCase levels are low, genetic testing is performed to identify GBA mutations.^2,3 Currently, the main treatment options for GD are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Patients receiving these treatments may still have poor outcomes due to the natural progression of the disease. Although new therapeutic developments of enzymes and substrate inhibitors have been made, research must proceed, and monitoring patients is of utmost importance in order to identify progression of GD.²

References

1. GBA gene – Genetics Home Reference – NIH. (2020). Retrieved July 8, 2020, from https://ghr.nlm.nih.gov/gene/GBA
2. Stirnemann, J. Ô., Belmatoug, N., Camou, F., Serratrice, C., Froissart, R., Caillaud, C., Levade, T., Astudillo, L., Serratrice, J., Brassier, A., Rose, C., De Villemeur, T. B., & Berger, M. G. (2017). A review of gaucher disease pathophysiology, clinical presentation and treatments. In International Journal of Molecular Sciences (Vol. 18, Issue 2, p. 441). MDPI AG. https://doi.org/10.3390/ijms18020441
3. Gaucher Disease – NORD (National Organization for Rare Disorders). (2018). Retrieved July 9, 2020, from https://rarediseases.org/rare-diseases/gaucher-disease/
4. Sidransky, E., Nalls, M. A., Aasly, J. O., Aharon-Peretz, J., Annesi, G., Barbosa, E. R., Bar-Shira, A., Berg, D., Bras, J., Brice, A., Chen, C.-M., Clark, L. N., Condroyer, C., De Marco, E. V., Dürr, A., Eblan, M. J., Fahn, S., Farrer, M. J., Fung, H.-C., … Ziegler, S. G. (2009). Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson’s Disease. New England Journal of Medicine, 361(17), 1651–1661. https://doi.org/10.1056/NEJMoa0901281

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