Normal Function
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.
Health Conditions Related to Genetic Changes
Fabry disease
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.
More About This Health ConditionOther Names for This Gene
- AGAL_HUMAN
- Agalsidase alfa
- Alpha-D-galactosidase A
- alpha-D-galactoside galactohydrolase
- Alpha-galactosidase
- alpha-Galactosidase A
- ceramidetrihexosidase
- GALA
- galactosidase, alpha
- Melibiase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Feldt-Rasmussen U, Rasmussen AK, Mersebach H, Rosenberg KM, Hasholt L, Sorensen SA. Fabry disease--a metabolic disorder with a challenge for endocrinologists? Horm Res. 2002;58(6):259-65. doi: 10.1159/000066443. Citation on PubMed
- Garman SC, Garboczi DN. The molecular defect leading to Fabry disease: structure of human alpha-galactosidase. J Mol Biol. 2004 Mar 19;337(2):319-35. doi: 10.1016/j.jmb.2004.01.035. Citation on PubMed
- Matsuzawa F, Aikawa S, Doi H, Okumiya T, Sakuraba H. Fabry disease: correlation between structural changes in alpha-galactosidase, and clinical and biochemical phenotypes. Hum Genet. 2005 Aug;117(4):317-28. doi: 10.1007/s00439-005-1300-5. Epub 2005 May 28. Citation on PubMed
- Mehta A, Hughes DA. Fabry Disease. 2002 Aug 5 [updated 2024 Apr 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1292/ Citation on PubMed
- Pastores GM, Lien YH. Biochemical and molecular genetic basis of Fabry disease. J Am Soc Nephrol. 2002 Jun;13 Suppl 2:S130-3. No abstract available. Citation on PubMed
- Schafer E, Baron K, Widmer U, Deegan P, Neumann HP, Sunder-Plassmann G, Johansson JO, Whybra C, Ries M, Pastores GM, Mehta A, Beck M, Gal A. Thirty-four novel mutations of the GLA gene in 121 patients with Fabry disease. Hum Mutat. 2005 Apr;25(4):412. doi: 10.1002/humu.9327. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.