Gaucher Disease 2011
Contents
Summary
Gaucher Disease is a lysosomal storage disease, which was first described by Philippe Gaucher in 1882. It is a genetic disease, which is caused by a recessive autosomal mutation in the gene GBA. It causes accumulation of glucosylceramide, because the enzyme glucocerebrosidase does not work. Therefore the patients show several symptomes which are described below. Respective to the severity and the symptomes of the disease, it is subdivided into three types.
The diagnosis is made by genetic testing or it can be detected by biochemical abnormalities (for example high alkaline phosphatase, angiotensin-converting enzyme, immunoglobulin levels). The treatment is only possible for type 1 and partially type 3 by an enzyme replacement therapy.
Phenotype
Gaucher Disease patients show various symptomes caused by the accumulation of glucosylceramide in the cells. The most common form of Gaucher Disease is Type 1, Type 2 is the rarest form and also the worst. Children who have Gaucher Disease Type 2 die at the age of two years.
Patients of all types show an enlarged spleen and liver and often have liver malfunction. They also have skeletal disorders, bone lesions and sometimes osteoporosis. Patients also have a swelling of the lymph nodes, low blood platelets and anemia. They have a brownish skin and yellow fatty deposits on the white of the eye. In type 3 and mainly in type 2 they show severe neurologic disorders.
Look at the image to see the different symptomes and their severity respective to the type of Gaucher Disease.
Cross-references
See also description of this disease in
Biochemical disease mechanism
In Gaucher Disease the protein Glycosylceramidase, also named Glucocerebrosidase, is mutated. It is located in the lysosome and involved in the sphingolipid metabolism. As an enzyme its function is to catalyze the breakdown of glucocerebroside into glucose and fat.
Cross-references
- KEGG: Sphingolipid metabolism
- KEGG: Gaucher disease
- MetaCyc: Function of Glycosylceramidase
- Uniprot: Glucosylceramidase
Structure of the protein
The protein beta-Glycosylceramidase consists of three domains. TODO
Cross-references
- PDB 2E9L (with glucose and fatty acids)
- PDBsum 2E9L
- PDB 2E9M (width galactose and fatty acids)
- PDBsum 2E9M
Mutations
Currently 303 mutations of the gene GBA are known. TODO
Current knowledge about mutations associated with the disease. - Separate into disease causing and neutral mutations.
Reference sequence
Which sequence does not cause the disease and is most often found in the population.
- Create a page for the reference sequence. -- These sequence pages will be the starting point for collecting prediction results and result discussions.
