This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison, Genetics 564
What is Gaucher disease?
Gaucher disease is the most common lysosomal storage disease and is inherited in an autosomal recessive fashion [1]. The disease is characterized by an accumulation of glucocerebrosides within cells [2]. In the vast majority of patients, the reduction of glucocerebrosidase (the enzyme required for the breakdown of glucocerebroside) activity is caused by mutations in the gene that codes for glucocerebrosidase [3]. In a few instances, glucocerebroside accumulates due to a lack of saposin C, a cohydrolase that is required in addition to glucocerebrosidase for the catabolism of glucocerebroside [3]. This website will focus on the gene that rarely causes Gaucher disease. The name of this gene is PSAP, and it encodes for the saposin C protein.
Inheritance of Gaucher disease
Gaucher disease is inherited in an autosomal recessive manner. This means that both parents must contain a copy of the mutated allele for the possibility of a having a child with the disease. The gene is located on an autosomal chromosome and is not sex linked. See Figure 1 one for further clarification.
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Different types of Gaucher disease
There are three types of Gaucher disease, the most common being Type one [2]. Type 1 can produce a broad range of symptoms that usually are the result of low blood cells and the affected spleen, liver, and bone marrow [2]. Types 2 and 3 have similar symptoms to Type 1, but also involve neurological damage [3]. The prevalence of Type 1 Gaucher disease is estimated to be 1:40,000 to 60,000 in the general population [4]. Ashkenazi Jews are much more likely to carry a defective allele and have a prevalence of 1:500 to 800 [4].
Management of Gaucher disease: enzyme replacement therapy
Current management for Gaucher disease involves intravenous injection of enzymes. There are currently three drugs approved by the FDA: imiglucerase, velaglucerase alfa, and taliglucerase alfo [5].
Sources Cited
[1] Chen, M and Wang, J. (2008) Gaucher Disease: Review of the Literature. Archives of Pathology & Laboratory Medicine,132, 851-853.
[2] Guggenbuhl P, Grosbois B, Gerard C. (2007). Gaucher DIsease. Joint Bone Spine, 75, 116-24. doi:10.1016/j.jbspin.2007.06.006
[3] Brady RO, Barton NW, Grabowski GA. (1993). The Role of Neurogenetics in Gaucher Disease.
Archives of Neurology, 50, 1212-1224. doi:10.1001/archneur.1993.00540110088009.
[4] Weinreb NJ, et al. (2008). Prevalence of Type 1 Gaucher Disease in the United States, Archives of Internal Medicine, 168(3), 326-327. doi:10.1001/archinternmed.2007.128.
[5] Zimran A, Elstein D. (2014). Management of Gaucher disease: enzyme replacement therapy, Pediatric Endocrinal Review, 12, 82-87.
Media Sources:
Youtube video: https://www.youtube.com/watch?v=camQrynzNIM
Inheritance Picture: http://ghr.nlm.nih.gov/handbook/illustrations/autorecessive
Picture of hepatosplenomegaly: http://health.allrefer.com/pictures-images/
Picture of skeleton with symptoms: http://becuo.com/gauchers-disease-diagram
[1] Chen, M and Wang, J. (2008) Gaucher Disease: Review of the Literature. Archives of Pathology & Laboratory Medicine,132, 851-853.
[2] Guggenbuhl P, Grosbois B, Gerard C. (2007). Gaucher DIsease. Joint Bone Spine, 75, 116-24. doi:10.1016/j.jbspin.2007.06.006
[3] Brady RO, Barton NW, Grabowski GA. (1993). The Role of Neurogenetics in Gaucher Disease.
Archives of Neurology, 50, 1212-1224. doi:10.1001/archneur.1993.00540110088009.
[4] Weinreb NJ, et al. (2008). Prevalence of Type 1 Gaucher Disease in the United States, Archives of Internal Medicine, 168(3), 326-327. doi:10.1001/archinternmed.2007.128.
[5] Zimran A, Elstein D. (2014). Management of Gaucher disease: enzyme replacement therapy, Pediatric Endocrinal Review, 12, 82-87.
Media Sources:
Youtube video: https://www.youtube.com/watch?v=camQrynzNIM
Inheritance Picture: http://ghr.nlm.nih.gov/handbook/illustrations/autorecessive
Picture of hepatosplenomegaly: http://health.allrefer.com/pictures-images/
Picture of skeleton with symptoms: http://becuo.com/gauchers-disease-diagram