Case 19 Glucosylceramidase beta and gaucher disease

What is Gaucher Disease?

Gaucher Disease is the most common lysosomal storage disease. It is an inherited disorder in which Glucosylceramidase builds up in the cells and organs such as the spleen, liver and bone marrow. There is three types of Gaucher Disease. Type 1 is the most common form in western countries affecting up to 95% of the overall patients. This type is treatable. Type 2 is much more rare and affects the brain stem. This type is very fatal and typically results in death within the first two years of life. Type 3 is the most common form worldwide, although it is rare in the United States and Europe. This type is moderately severe and has symptoms from both type one and type three. However, treatment is an option for type 3 of gaucher disease.

What is the gene in which the mutation occurs in? What protein does this gene create?

The gene in which the mutation occurs in is the glucosylceramidase gene, also know as the GBA gene. The GBA gene created the glucosylceramidase beta [Homo Sapiens] protein. The mutation in this gene causes the activity of the GBA gene to be greatly reduced or stopped entirely in cells. This causes GBA to not be broken down right which in return causes GBA and anything similar to build up in the organs and cause damage.

Location of the GBA Gene

How and when was Gaucher Disease first discovered/documented?

Gaucher Disease was discovered in 1943 by a scientist named A. Aghion, a French chemist. He discovered the chemical "Glucocerebroside" (Also know as Glucosylceramidase) that was build up in enlarged livers and spleens.

Enlarged cells in the spleen of a patient with Gaucher Disease

What is the incidence rate of Gaucher Disease in the United States? What is it in the world?

Gaucher Disease affects 1 in 40,000 to 1 in 100,000 successful births in the world. Gaucher Disease is also very rare in the United States, type 3 being especially rare in the United States and Type one being the most common.

Are any specific populations of people affected by Gaucher Disease more than others?

Gaucher Disease is most common in the Jews of Ashkenazi, who are located in eastern Europe. Within this population every 1 in 450 births, Gaucher Disease occurs, and 1 in 10 people carry the gene mutation which causes Gaucher Disease.

What are the Symptoms of Gaucher Disease?

Type 1 symptoms include spleen and liver enlargement, low blood count, bleeding problems due to the blood clotting process not functioning correctly because of low blood count, and bone problems such as fragile bones and bone pain.

Type 2 symptoms are very severe and include the same symptoms as type 1 and brain damage that gets worse as time goes on. Other symptoms include poor development, seizures, spasticity, poor ability to such and swallow and enlarged liver and spleen. Type 2 is fatal and results in death within the first two years of life.

Type 3 symptoms are more gradual and get worse over time. Symptoms can include seizures, skeletal irregularities, eye movement disorders, cognitive problems, poor coordination, enlarged liver and spleen, respiratory problems and blood disorders.

Enlarged Spleen and Liver

How is Gaucher Disease Diagnosed and Treated?

Gaucher is diagnosed through a blood test know as a BGL test which looks at enzyme activity. Then a bone marrow test could be done to rule out cancers as the cause. A genetic test could also be done to show if a patient is a carrier of the disease.

There are two forms of treatment for Gaucher Disease. The first one is Enzyme Replacement Therapy (ERT.) This treatment is for mainly Type 1 but can also treat some symptoms of Type 3. ERT involves balancing a GCase enzymes with a modified version of the normal human enzyme, allowing glucocerebroside to be broken down. Patients must receive an infusion every two weeks for this therapy.

The second form of treatment for Gaucher Disease is know as Substrate Reduction Therapy (SRT.) This treatment is also for mainly type 1 but also helps with symptoms of type 3. SRT reduces the amount of glucocerebroside produced by the body, making it easier for the body to break down the enzyme. This treatment is an oral medication.

What is the prognosis for a patient diagnosed with Gaucher Disease?

Patients Diagnosed with type 1 of Gaucher Disease can live a full life with treatment. Patients Diagnosed with type 2 typically die before the age of two and most children diagnosed with Gaucher disease die by the age of five. Patients Diagnosed with type 3 can live into adulthood with treatment.

What is the genetic pattern of inheritance?

Gaucher disease is an autosomal recessive disorder, meaning the child must receive the gene from both parents in order to develop Gaucher Disease.

Autosomal Recessive Gene Required for Gaucher Disease

What is the current research being conducted for Gaucher Disease?

Currently scientists are conducting research on the number of the mutations in the GBA gene and they have identified nearly 300 mutations. Scientists have also been researching disease variability and the link between Gaucher Disease and Parkinson Disease. They have discovered that some patients with Parkinson Disease also have mutations in the GCcase gene. Scientists have also been studying the role of protein activity in gaucher disease and have recently found that improper protein folding is found in low GCcase enzyme. Also, scientists found that the balance of the GCcase enzyme and alpha-synuclein play a big role in the mutation because they help the body's proteins function properly.

Donate- National Gaucher Foundation

http://www.gaucherdisease.org/donate/

Works Cited

Autosomal Recessive Gene. Gaucher Disease, 2017, www.geneticsofpregnancy.com/images/Gaucher_disease.gif. Accessed 4 Feb. 2017.

“Brian’s Story: Finding a Cure for Type 1 Gaucher.” YouTube, Google, 1 Nov. 2016, www.youtube.com/watch?v=h_M9yEPcJPw. Accessed 4 Feb. 2017.

“Donate.” National Gaucher Foundation, 2017, www.gaucherdisease.org/donate/. Accessed 4 Feb. 2017.

“Dr. Roscoe Brady and Gaucher Disease.” Researching Disease, NIH History, 2017, history.nih.gov/exhibits/gaucher/docs/page_03.html. Accessed 4 Feb. 2017.

Enlarged Cells in the Spleen of a Person with Gaucher Disease. Researching Disease, NIH History, 2017, history.nih.gov/exhibits/gaucher/assets/images/gaucherdisease_lg.jpg. Accessed 4 Feb. 2017.

Enlarged Spleen and Liver. Chromosomal Aberrations/Mutations, 2017, projectict00.weebly.com/uploads/2/4/2/0/24201934/7679674.jpg. Accessed 4 Feb. 2017.

“Gaucher Disease.” Genetics Home Reference, U.S. Department of Health and Human Services, 31 Jan. 2017, ghr.nlm.nih.gov/condition/gaucher-disease. Accessed 4 Feb. 2017.

“Gaucher Disease.” Medline Plus, edited by Chad Haldeman-Englert, U.S. Library of Medication, 5 Jan. 2017, medlineplus.gov/ency/article/000564.htm. Accessed 4 Feb. 2017.

“Gaucher Disease Treatment.” Gaucher Disease Foundation, 2017, www.gaucherdisease.org/gaucher-diagnosis-treatment/treatment/. Accessed 4 Feb. 2017.

“Gaucher Disease Type 1.” National Gaucher Foundation, 2017, www.gaucherdisease.org/about-gaucher-disease/what-is/type-1/. Accessed 4 Feb. 2017.

“Gaucher Disease Type 2 and 3.” National Gaucher Foundation, 2017, www.gaucherdisease.org/about-gaucher-disease/what-is/type-2-3/. Accessed 4 Feb. 2017.

Location of GBA Gene. Genetics Home Reference, U.S. Department of Health and Human Services, 31 Jan. 2017, ghr.nlm.nih.gov/gene/GBA/location.png. Accessed 4 Feb. 2017.

“Recently Published Research.” National Gaucher Foundation, 2017, www.gaucherdisease.org/research/recent-research/. Accessed 4 Feb. 2017.

“Testing for Gaucher Disease.” National Gaucher Foundation, National Gaucher Foundaton, 2017, www.gaucherdisease.org/about-gaucher-disease/what-is/type-2-3/. Accessed 4 Feb. 2017.

“What is Gaucher Disease?” National Gaucher Fondation, 2017, www.gaucherdisease.org/about-gaucher-disease/what-is/. Accessed 31 Jan. 2017.

“What is Gaucher Disease?” YouTube, uploaded by Spotlight On Gaucher, Google, 4 Nov. 2015, www.youtube.com/watch?v=j_WcSgcK1Tw. Accessed 4 Feb. 2017.

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