Normal Function
The ARSA gene provides instructions for making the enzyme arylsulfatase A. This enzyme is located in cellular structures called lysosomes, which are the cell's recycling centers. Within lysosomes, arylsulfatase A helps process substances known as sulfatides. Sulfatides are a subgroup of sphingolipids, a category of fats that are important components of cell membranes. Sulfatides are abundant in the nervous system's white matter, consisting of nerve fibers covered by myelin. Myelin, made up of multiple layers of membranes, insulates and protects nerves.
Health Conditions Related to Genetic Changes
Metachromatic leukodystrophy
More than 110 mutations that cause metachromatic leukodystrophy, a disorder that causes deterioration of nervous system functions, have been identified in the ARSA gene. These mutations greatly reduce the activity of arylsulfatase A. Severe disruption in arylsulfatase A activity interferes with the breakdown of sulfatides. As a result, these substances can accumulate to toxic levels in the nervous system. The buildup of sulfatides gradually destroys the cells that produce myelin, the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to the loss of white matter (leukodystrophy) and impairment of nervous system function, resulting in the signs and symptoms of metachromatic leukodystrophy.
In some cases, individuals with very low arylsulfatase A activity show no signs or symptoms of metachromatic leukodystrophy. This condition, called pseudoarylsulfatase deficiency, seems to be caused by specific variations of the ARSA gene. These variations are present in as many as 5 to 10 percent of Europeans and North Americans.
More About This Health ConditionOther Names for This Gene
- ARSA_HUMAN
- cerebroside 3-sulfatase
- Cerebroside-3-sulfate 3-sulfohydrolase
- Cerebroside-Sulfatase
- MLD
- sulfatidase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Basic Neurochemistry (sixth edition, 1999): Lysosomal Disease
- Cesani M, Capotondo A, Plati T, Sergi LS, Fumagalli F, Roncarolo MG, Naldini L, Comi G, Sessa M, Biffi A. Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophy. Hum Mutat. 2009 Oct;30(10):E936-45. doi: 10.1002/humu.21093. Citation on PubMed
- Essentials of Glycobiology (first edition, 1999): Glycosphingolipid Degradation
- Gieselmann V, Krageloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics. 2010 Feb;41(1):1-6. doi: 10.1055/s-0030-1253412. Epub 2010 Jun 22. Citation on PubMed
- Grossi S, Regis S, Rosano C, Corsolini F, Uziel G, Sessa M, Di Rocco M, Parenti G, Deodato F, Leuzzi V, Biancheri R, Filocamo M. Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles. Hum Mutat. 2008 Nov;29(11):E220-30. doi: 10.1002/humu.20851. Citation on PubMed
- Lugowska A, Ploski R, Wlodarski P, Tylki-Szymanska A. Molecular bases of metachromatic leukodystrophy in Polish patients. J Hum Genet. 2010 Jun;55(6):394-6. doi: 10.1038/jhg.2010.25. Epub 2010 Mar 26. Citation on PubMed
- Poeppel P, Habetha M, Marcao A, Bussow H, Berna L, Gieselmann V. Missense mutations as a cause of metachromatic leukodystrophy. Degradation of arylsulfatase A in the endoplasmic reticulum. FEBS J. 2005 Mar;272(5):1179-88. doi: 10.1111/j.1742-4658.2005.04553.x. Citation on PubMed
- Rauschka H, Colsch B, Baumann N, Wevers R, Schmidbauer M, Krammer M, Turpin JC, Lefevre M, Olivier C, Tardieu S, Krivit W, Moser H, Moser A, Gieselmann V, Zalc B, Cox T, Reuner U, Tylki-Szymanska A, Aboul-Enein F, LeGuern E, Bernheimer H, Berger J. Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. Neurology. 2006 Sep 12;67(5):859-63. doi: 10.1212/01.wnl.0000234129.97727.4d. Citation on PubMed
- Shukla P, Vasisht S, Srivastava R, Gupta N, Ghosh M, Kumar M, Sharma R, Gupta AK, Kaur P, Kamate M, Gulati S, Kalra V, Phadke S, Singhi P, Dherai AJ, Kabra M. Molecular and structural analysis of metachromatic leukodystrophy patients in Indian population. J Neurol Sci. 2011 Feb 15;301(1-2):38-45. doi: 10.1016/j.jns.2010.11.007. Epub 2010 Dec 16. Citation on PubMed
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