GLA

Reviewed March 2007

What is the official name of the GLA gene?

The official name of this gene is “galactosidase, alpha.”

GLA is the gene's official symbol. The GLA gene is also known by other names, listed below.

What is the normal function of the GLA gene?

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.

How are changes in the GLA gene related to health conditions?

Fabry disease - caused by mutations in the GLA gene

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.

Where is the GLA gene located?

Cytogenetic Location: Xq22

Molecular Location on the X chromosome: base pairs 100,652,778 to 100,663,000

The GLA gene is located on the long (q) arm of the X chromosome at position 22.

More precisely, the GLA gene is located from base pair 100,652,778 to base pair 100,663,000 on the X chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about GLA?

You and your healthcare professional may find the following resources about GLA helpful.

Educational resources - Information pages
- Basic Neurochemistry (sixth edition, 1999): Lysosomal Disease (http://www.ncbi.nlm.nih.gov/books/NBK28215/)
- Neuromuscular Disease Center, Washington University (http://neuromuscular.wustl.edu/sensory-pain.html)
Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1292/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for GLA (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=2717%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((Agalsidase%20alfa%5BTIAB%5D)%20OR%20(Alpha-D-galactosidase%20A%5BTIAB%5D)%20OR%20(alpha-D-galactoside%20galactohydrolase%5BTIAB%5D)%20OR%20(alpha-Galactosidase%5BTIAB%5D)%20OR%20(Melibiase%5BTIAB%5D)%20OR%20(ceramidetrihexosidase%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/300644)
Research Resources - Tools for researchers
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/2717)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=2717)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=4296)

What other names do people use for the GLA gene or gene products?

AGAL_HUMAN
Agalsidase alfa
Alpha-D-galactosidase A
alpha-D-galactoside galactohydrolase
Alpha-galactosidase
alpha-Galactosidase A
ceramidetrihexosidase
GALA
Melibiase

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding GLA?

amino acid ; cell ; digestive ; enzyme ; gene ; molecule ; mutation ; nervous system ; protein

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/2717)
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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12446988?dopt=Abstract)
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. (http://www.ncbi.nlm.nih.gov/pubmed/15003450?dopt=Abstract)
Gene Review: Fabry Disease (http://www.ncbi.nlm.nih.gov/books/NBK1292/)
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. Epub 2005 May 28. (http://www.ncbi.nlm.nih.gov/pubmed/15924232?dopt=Abstract)
Pastores GM, Lien YH. Biochemical and molecular genetic basis of Fabry disease. J Am Soc Nephrol. 2002 Jun;13 Suppl 2:S130-3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12068024?dopt=Abstract)
Schäfer 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. (http://www.ncbi.nlm.nih.gov/pubmed/15776423?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

GLA