Aspartoacylase (Canavan disease) (ASPA)

The official name of this gene is “aspartoacylase (Canavan disease).”

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

The ASPA gene provides instructions for making an enzyme called aspartoacylase. In the brain, this enzyme breaks down a compound called N-acetyl-L-aspartic acid (NAA) into aspartic acid (an amino acid that is a building block of many proteins) and another molecule called acetic acid.

The cycle of production and breakdown of NAA appears to be critical for maintaining the brain's white matter, which consists of nerve fibers covered by myelin. Myelin is the fatty substance that insulates and protects nerves. Although the precise function of NAA is unknown, it is probably essential for making certain fats (lipids) that are used to produce myelin. Researchers believe that NAA may also play a role in transporting molecules of water out of nerve cells.

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

Canavan disease - caused by mutations in the ASPA gene More than 55 mutations in the ASPA gene are known to cause Canavan disease. Two specific mutations cause most cases of the disease in people of Ashkenazi (eastern and central European) Jewish descent. One of these mutations changes a single protein building block (amino acid) in aspartoacylase. Specifically, this mutation replaces the amino acid glutamic acid with the amino acid alanine at position 285 of the enzyme (written as Glu285Ala or E285A). The other common mutation, which is written as Tyr231Ter or Y231X, prematurely stops protein production and leads to an abnormally small, nonfunctional version of the enzyme.

A different mutation is most common in people who are not of Ashkenazi Jewish descent. This mutation substitutes the amino acid glutamic acid for the amino acid alanine at position 305 of aspartoacylase (written as Ala305Glu or A305E).

Mutations in the ASPA gene reduce or eliminate the activity of aspartoacylase, which prevents the normal breakdown of NAA in the brain. Recent studies suggest that if NAA is not broken down properly, the resulting chemical imbalance may interfere with the formation of myelin as the nervous system develops. A buildup of NAA also leads to the progressive destruction of existing myelin around nerve cells. Nerve fibers without this protective covering malfunction and die, damaging the brain and causing the serious signs and symptoms of Canavan disease.

Where is the ASPA gene located?

Cytogenetic Location: 17pter-p13

Molecular Location on chromosome 17: base pairs 3,326,045 to 3,349,449

The ASPA gene is located on the short (p) arm of chromosome 17 between the end (terminus) of the arm and position 13.

More precisely, the ASPA gene is located from base pair 3,326,045 to base pair 3,349,449 on chromosome 17.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about ASPA?

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

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals

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

• PubMed - Recent literature
• OMIM - Genetic disorder catalog
• Research Resources - Tools for researchers (3 links)

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

• ACY2
• ACY2_HUMAN
• Aminoacylase 2
• aminoacylase II
• ASP
• aspartoacylase
• aspartoacylase (aminoacylase 2, Canavan disease)
• N-acyl-L-aspartate amidohydrolase

See How are genetic conditions and genes named? in the Handbook.

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

• What is DNA?
• What is a gene?
• How do genes direct the production of proteins?
• How can gene mutations affect health and development?

These links provide additional genetics resources that may be useful.

• Genetics education
• Human Genome Project
• Resources for Genetic Researchers

What glossary definitions help with understanding ASPA?

acids ; amino acid ; Ashkenazi Jewish ; cell ; compound ; enzyme ; gene ; lipid ; molecule ; mutation ; nerve cell ; nervous system ; protein ; sign ; symptom ; white matter

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References

These sources were used to develop the Genetics Home Reference gene summary on the ASPA gene.

• Baslow MH. Brain N-acetylaspartate as a molecular water pump and its role in the etiology of Canavan disease: a mechanistic explanation. J Mol Neurosci. 2003;21(3):185-90. Review. PubMed citation
• Baslow MH. Evidence supporting a role for N-acetyl-L-aspartate as a molecular water pump in myelinated neurons in the central nervous system. An analytical review. Neurochem Int. 2002 Apr;40(4):295-300. Review. PubMed citation
• Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr. Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):456-61. Epub 2006 Dec 28. PubMed citation
• Hershfield JR, Pattabiraman N, Madhavarao CN, Namboodiri MA. Mutational analysis of aspartoacylase: implications for Canavan disease. Brain Res. 2007 May 7;1148:1-14. Epub 2007 Mar 3. PubMed citation
• Leone P, Janson CG, Bilaniuk L, Wang Z, Sorgi F, Huang L, Matalon R, Kaul R, Zeng Z, Freese A, McPhee SW, Mee E, During MJ, Bilianuk L. Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Ann Neurol. 2000 Jul;48(1):27-38. PubMed citation
• Madhavarao CN, Arun P, Moffett JR, Szucs S, Surendran S, Matalon R, Garbern J, Hristova D, Johnson A, Jiang W, Namboodiri MA. Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5221-6. Epub 2005 Mar 22. PubMed citation
• Matalon R, Rady PL, Platt KA, Skinner HB, Quast MJ, Campbell GA, Matalon K, Ceci JD, Tyring SK, Nehls M, Surendran S, Wei J, Ezell EL, Szucs S. Knock-out mouse for Canavan disease: a model for gene transfer to the central nervous system. J Gene Med. 2000 May-Jun;2(3):165-75. PubMed citation
• Namboodiri AM, Peethambaran A, Mathew R, Sambhu PA, Hershfield J, Moffett JR, Madhavarao CN. Canavan disease and the role of N-acetylaspartate in myelin synthesis. Mol Cell Endocrinol. 2006 Jun 27;252(1-2):216-23. Epub 2006 May 2. Review. PubMed citation