The GLA gene provides instructions for making an enzyme called alpha-galactosidase A. This enzyme is active in lysosomes, which are structures that act as recycling centers within cells. Lysosomes use digestive enzymes to process worn-out cell components and recycle usable parts.
Alpha-galactosidase A breaks down a molecule called globotriaosylceramide, which consists of three sugars attached to a fatty substance. This molecule is degraded as part of the normal recycling of old red blood cells (erythrocytes) and other types of cells.
More than 370 mutations in the GLA gene have been identified in people with Fabry disease. Most of these genetic changes are unique to single families. The most common type of mutation changes a single protein building block (amino acid) in alpha-galactosidase A. Other mutations delete part of the GLA gene, insert extra genetic material into the gene, or insert a premature stop signal in the gene's instructions for making alpha-galactosidase A. Alterations in the GLA gene produce an abnormal version of the enzyme that is unable to break down globotriaosylceramide effectively. As a result, this substance builds up in the body's cells, particularly cells lining blood vessels in the skin and cells in the kidneys, heart, and nervous system. The progressive accumulation of globotriaosylceramide damages these cells, leading to the varied signs and symptoms of Fabry disease.
Mutations that eliminate the activity of the alpha-galactosidase A enzyme lead to the severe, classic form of Fabry disease, which typically begins in childhood. Mutations that reduce but do not completely eliminate the enzyme's activity usually cause milder, late-onset forms of the disorder.
- Agalsidase alfa
- Alpha-D-galactosidase A
- alpha-D-galactoside galactohydrolase
- alpha-Galactosidase A
- galactosidase, alpha