Fabry Disease 2011

Summary

Fabry disease is a rare genetic disease, that is inherited via the X-chromosome and causes a defect in the gene GAL. It is a Lysosomal Storage Disease and therefor causes a wide range of symptoms. The disease is named after the German Johannes Fabry, who described the disease in 1898 simultaneous with William Anderson from UK.

Phenotype

Symptoms

As the effects caused by the enzymatic disfunction summarize over time, the symptoms evolve progressive.

Childhood

• Pain and burning in the hands and feet
• Impaired sweating
• Psychological and social issues
• Low tolerance for exercise
• Eye abnormalities

Adolescence

• Dark red skin rashes (angiokeratomas)
• Fatigue
• Gastrointestinal problems

Adulthood

• Heart problems
• Kidney problems
• Nervous system problems
• Hearing problems

Cross-references

See also description of this disease in

• Wikipedia
• HGMD
• OMIM:Fabry Disease
• PubMed
• NINDS
• GHR
• NCBI Bookshelf

... (see databases in "resources")

α-galactosidase A

Gene

The location of the gene GLA on the X chromosome.

The protein α-galactosidase A is encoded by the gene GLA, which is locacted on the X chromosome (gene map locus: Xq22). The gene has an overall length of 10,222 nucleotides and consist of 7 exons (1,290 nucleotides) and 6 introns (8,932 nucleotides).

Cross-references

• NCBI: GLA
• OMIM: GLA
• KEGG: GLA
• Genetics Home Reference: GLA

Protein

Representation of the protein α-galactosidase A.

α-galactosidase A is a homodimeric protein that consist of 398 amino acids. It is a glycosidase (EC number: 3.2.1.22) and hydrolyses O- and S-glycosidic bonds of glycolipids.

Cross-references

• KEGG: EC 3.2.1.22
• MetaCyc: α-Galactosidase A
• PDB: 1R47
• UniProt: α-galactosidase A
• Wikipedia: α-galactosidase A

Biochemical disease mechanism

Glycosphingolipid biosynthesis of Homo sapiens. The disease associated enzyme is highlighted in red.

The hydrolysation of globotriaosylceramide (GL3) to lactosylceramide (GL2) and galactose is catalyzed by the protein α-galactosidase A.

Mutations of the gene GLA influence the enzyme α-galactosidase A. These mutations can affect the synthesis, kinetic properties and stability of the enzyme which leads to an decreased enzyme activity. Hence the catabolization of glycosphingolipids is not done properly which is especially the case for the breakdown of globotriaosylceramide (GL3) to lactosylceramide (GL2) and galactose. The accumulation of the glycosphingolipids leads to the progressively arising symptoms of the Fabry disease. Since the α-galactosidase A is located in the lysosome Fabry disease is categorized as an lysosomal storage disorder.

Cross-references

• KEGG: Fabry Disease
• KEGG: Glycosphingolipid biosynthesis

Mutations

Current knowledge about mutations associated with the disease. - Separate into disease causing and neutral mutations. -- These sequence pages will be the starting point for collecting prediction results and result discussions.

Reference sequence

• Nucleotide sequence
• Amino acid sequence