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Canavan Disease

Synonyms: ASPA Deficiency, Aspartoacylase Deficiency

, MD, PhD and , PhD, RD.

Author Information

Initial Posting: ; Last Update: August 11, 2011.


Clinical characteristics.

Neonatal/infantile (severe) Canavan disease is characterized by macrocephaly, lack of head control, and developmental delays usually noted by age three to five months. As children get older hypotonia becomes severe and failure to achieve independent sitting, ambulation, or speech become apparent. Hypotonia eventually changes to spasticity. Assistance with feeding becomes necessary. Life expectancy is usually into the teens. Mild/juvenile Canavan disease is characterized by mild developmental delay that can go unrecognized. Head circumference may be normal.


The diagnosis of neonatal/infantile Canavan disease relies on demonstration of very high concentration of N-acetylaspartic acid (NAA) in the urine. In mild/juvenile Canavan disease NAA may only be slightly elevated; thus, the diagnosis relies on molecular genetic testing of ASPA, the gene encoding the enzyme aspartoacylase.


Treatment of manifestations: Neonatal/infantile Canavan disease: Treatment is supportive and directed to providing adequate nutrition and hydration, managing infectious diseases, and protecting the airway. Physical therapy minimizes contractures and maximizes motor abilities and seating posture; special education programs enhance communication skills. Seizures are treated with antiepileptic drugs. Gastrostomy may be needed to maintain adequate food intake and hydration when swallowing difficulties exist.

Surveillance: Neonatal/infantile Canavan disease: Follow up every six months to evaluate developmental status and evidence of any new problems.

Genetic counseling.

Canavan disease is inherited in an autosomal recessive manner. Each pregnancy of a couple in which both partners are heterozygous for a pathogenic variant in ASPA has a 25% chance of resulting in a child with Canavan disease, a 50% chance of resulting in a child who is an asymptomatic carrier, and a 25% chance of resulting in a child who is unaffected and not a carrier. Carrier testing is available on a population basis for individuals of Ashkenazi Jewish heritage. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible when the pathogenic variants in the family are known. For couples in which one partner is known to be a carrier and the carrier status of the other is unknown, prenatal testing can be performed by measuring the concentration of NAA in amniotic fluid at 16 to 18 weeks' gestation.


Clinical Diagnosis

The triad of hypotonia, macrocephaly, and head lag in an infant after age three to five months raises suspicion of neonatal/infantile (severe) Canavan disease. Neuroimaging studies reveal leukodystrophy.

In individuals with mild/juvenile Canavan disease, neuroimaging may not be helpful.


N-Acetylaspartic acid (NAA)

  • Urine. The concentration of NAA in the urine can be measured using gas chromatography-mass spectrometry (GC-MS) [Michals & Matalon 2011]. Control values in one series (n=48) were 23.5±16.1 µmol/mmol creatinine.
    • In neonatal/infantile (severe) Canavan disease the mean concentration of NAA (n=117) was 1,440.5±873.3 µmol/mmol creatinine.
    • In mild/juvenile Canavan disease, mild elevation of NAA may be found, (n=2) 106 µmol/mmol creatinine.
      Note: Although NAA concentration is also elevated in the blood and CSF of children with neonatal/infantile (severe) Canavan disease, the number of affected individuals evaluated to date is small [Michals & Matalon 2011].
  • Amniotic fluid. The concentration of NAA can be measured in the amniotic fluid by stable-isotope dilution and GC-MS or by liquid chromatography tandem mass spectrometry [Bennett et al 1993, Al-Dirbashi et al 2009]. NAA concentration in amniotic fluid was 0.30-2.55 µmol/L in controls and 8.68 µmol/L in an affected pregnancy [Bennett et al 1993].

Aspartoacylase enzyme activity

  • Skin fibroblasts. Although aspartoacylase enzyme activity can be assayed in cultured skin fibroblasts, it may not be reliable because the activity varies with culture conditions.
    • Individuals with severe Canavan disease often have unmeasurable enzyme activity.
    • Carriers of alleles associated with severe Canavan disease have about one-half normal enzyme activity [Matalon et al 1993].
  • White blood cells and thrombocytes. Aspartoacylase enzyme activity is not detectable in white blood cells or platelets.
  • Amniocytes/CVS. Aspartoacylase enzyme activity is extremely low in normal amniocytes and chorionic villus sampling (CVS). Enzyme activity cannot be relied upon for prenatal testing [Bennett et al 1993].

Molecular Genetic Testing

Gene. ASPA is the only gene in which pathogenic variants are known to cause Canavan disease.

Clinical testing

Table 1.

Molecular Genetic Testing Used in Canavan Disease

GeneTest MethodVariants DetectedVariant Detection Frequency by Test Method 1
Ashkenazi JewishNon-Ashkenazi Jewish
ASPATargeted analysis for pathogenic variantsPanel 2p.Glu285Ala, p.Tyr231Ter98%3%
Sequence analysis 3Sequence variantsNA87%
Deletion/duplication analysis 4Large (multi)exon deletions/duplicationsNAUnknown (<10%)

NA = not applicable


The ability of the test method used to detect a variant that is present in the indicated gene


All laboratories use at least a two-variant panel for the Ashkenazi Jewish pathogenic variants; many laboratories use a three-variant panel, and a few use a four-variant panel.


Examples of variants detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site variants.


Testing that identifies exon or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

Testing Strategy

To confirm/establish the diagnosis in a proband with neonatal/infantile (severe) Canavan disease

To confirm/establish the diagnosis in a proband with mild/juvenile Canavan disease

  • Neuroimaging usually does not indicate leukodystrophy.
  • Concentration of NAA in the urine is slightly elevated.
  • Diagnosis must be confirmed by ASPA molecular genetic testing in the order described above.

Carrier testing

  • Testing for at-risk relatives requires prior identification of the pathogenic variants in the family.
  • Population screening for Ashkenazi Jewish individuals of reproductive age is recommended [ACOG Committee on Genetics 2009] and typically includes evaluation for the two pathogenic variants common in the Ashkenazi Jewish population.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the pathogenic variants in the family. Note: When the family-specific pathogenic variants are not known, prenatal diagnosis of Canavan disease can be accomplished by measuring the concentration of NAA in amniotic fluid.

Clinical Characteristics

Clinical Description

Neonatal/Infantile (Severe) Canavan Disease

Most individuals with Canavan disease have the neonatal/infantile form. Although these infants appear normal early in life, by age three to five months macrocephaly, lack of head control, and developmental delays become apparent. Developmental delay becomes more obvious with increasing age. Children with neonatal/infantile (severe) Canavan disease are especially delayed in their motor skills and are not able to sit, stand, walk, or talk. They learn to interact socially, laugh and smile, reach for objects, and raise their heads in the prone position. They are sometimes irritable. As they get older, hypotonia gives way to spasticity.

Optic atrophy is present in many children with neonatal/infantile (severe) Canavan disease. However, they are still able to visually track objects. Hearing is usually not impaired.

As they get older, children with neonatal/infantile (severe) Canavan disease may experience sleep disturbance, seizures, and feeding difficulties. They may require assisted feeding through a nasogastric tube or by a permanent gastrostomy.

The life expectancy is variable; some children die in the first few years of life, while others survive into their teens or beyond, depending on the clinical course of their disease as well as on the medical and nursing care provided.

Mild/Juvenile Canavan Disease

Children with mild/juvenile Canavan disease may have normal or mildly delayed speech or motor development early in life. If they have a diagnostic work-up for these delays, slightly elevated urinary NAA may be identified and indicate the diagnosis. Generally, these children attend regular school and may benefit from speech therapy or tutoring as needed.


Neonatal/infantile (severe) Canavan disease. CT or MRI performed in infancy may be interpreted as normal [Matalon & Michals-Matalon 2000]. Diffuse, symmetric white matter changes are observed in the subcortical areas and in the cerebral cortex; involvement of the cerebellum and brain stem is less marked [Matalon et al 1995].

Ultrasonography shows white matter echogenicity that differs from that of normal brain [Breitbach-Faller et al 2003].

Mild/juvenile Canavan disease. Brain MRI does not show general white matter disease. Brain MRI on many children with Canavan disease demonstrates increased signal intensities in the basal ganglia [Surendran et al 2003, Yalcinkaya et al 2005, Michals & Matalon 2011]. Similar changes are observed on MRI of the brain of individuals with mitochondrial diseases [Surendran et al 2003, Tacke et al 2005, Kurczynski & Victorio 2011, Michals & Matalon 2011].


In neonatal/infantile Canavan disease subcortical spongy degeneration is observed. Electron microscopy (EM) reveals swollen astrocytes and distorted mitochondria.

Genotype-Phenotype Correlations

Strong genotype-phenotype correlations in Canavan disease have emerged since the measurement of N-acetylaspartic acid (NAA) in the urine and molecular genetic testing of ASPA have become routine.

Neonatal/Infantile (Severe) Canavan Disease

Individuals homozygous for the p.Tyr231Ter pathogenic variant (who have no enzyme activity) cannot be clinically distinguished from individuals homozygous for the p.Glu285Ala pathogenic variant (who have some residual enzyme activity).

The clinical phenotype in individuals homozygous for the p.Ala305Glu pathogenic variant, most commonly observed in non-Jews (who have no residual enzyme activity), is similar to that observed in individuals homozygous for one of the two pathogenic variants commonly found in the Ashkenazi Jewish population [Matalon & Michals-Matalon 1998].

The clinical phenotype in individuals homozygous or compound heterozygous for a large (i.e., multiexon or whole-gene) deletion is severe.

Mild/Juvenile Canavan Disease

Mild/juvenile Canavan disease is associated with at least one "mild" pathogenic variant (p.Tyr288Cys, p.Arg71His, or p.Pro257Arg) with residual ASPA enzyme activity. Individuals are usually heterozygous with one mild variant and one severe variant [Surendran et al 2003, Yalcinkaya et al 2005, Kurczynski & Victorio 2011, Michals & Matalon 2011].

"Mild" variants are now more readily recognized by their manifestations of slight increase of NAA in the urine, atypical MRI findings, and associated minor learning difficulties [Surendran et al 2003, Tacke et al 2005, Kurczynski & Victorio 2011, Michals & Matalon 2011].


Other names for neonatal/infantile (severe) Canavan disease that are no longer in use include:


While Canavan disease occurs in all ethnic groups, most reported individuals are of Ashkenazi Jewish origin.

Carrier frequency has varied depending on the source of samples:

The carrier rate in non-Jews is not known; however, it is assumed to be much lower than the carrier rate in the Ashkenazi Jewish population.

Differential Diagnosis

Other neurodegenerative disorders of infancy that are associated with a normal or large head size include Alexander disease, Tay-Sachs disease, metachromatic leukodystrophy, and glutaricacidemia type 1. Laboratory testing or molecular genetic testing can be used to distinguish neonatal/infantile (severe) Canavan disease from these disorders.

Spongy degeneration of the brain can be found in viral infections, in mitochondrial disorders, particularly Leigh syndrome (see also Mitochondrial Disorders Overview), and in metabolic disorders such as glycine encephalopathy (nonketotic hyperglycinemia).

Mild/juvenile Canavan disease may be misdiagnosed as a mitochondrial disorder (see Mitochondrial Disorders Overview).


Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with neonatal/infantile (severe) Canavan disease, the following evaluations are recommended:

  • Brain MRI
  • Developmental assessment
  • Nutritional assessment

Treatment of Manifestations

Neonatal/infantile Canavan disease

• Treatment is supportive and directed to providing adequate nutrition and hydration, managing infectious diseases, and protecting the airway.

  • Children benefit from physical therapy to minimize contractures and to maximize abilities and seating posture, from other therapies to enhance communication skills (especially in those with a more gradual clinical course), and from early intervention and special education programs.
  • Seizures may be treated with antiepileptic drugs (AEDs).
  • A feeding gastrostomy may be required to maintain adequate intake and hydration in the presence of swallowing difficulties.
  • Diamox® seems to reduce intracranial pressure.
  • Botox® injections may be used to relieve spasticity.

Mild/juvenile Canavan disease. These individuals may require speech therapy or tutoring but require no special medical care.

Prevention of Secondary Complications

Neonatal/infantile Canavan disease

  • Contractures and decubiti need to be prevented by exercise and position changes.
  • Feeding difficulties and seizures increase the risk of aspiration, which can be reduced with use of a G-tube for feeding.


Neonatal/infantile Canavan disease. Follow up at six-month intervals to evaluate developmental status and evidence of any new problems is suggested.

Mild/juvenile Canavan disease. Annual routine follow up is indicated.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation


  • Gene transfer to the brains of two children with Canavan disease using a nonviral vector was well tolerated [Leone et al 2000, Janson et al 2002]. Some biochemical, radiologic, and clinical changes may have occurred; however, the children continued to follow the course of those with untreated Canavan disease.
  • In ten children with Canavan disease, multisite injection with AAV2 as the vector for ASPA was well tolerated [McPhee et al 2006]. Three developed AAV2 neutralizing antibodies. No children improved.
  • Lithium citrate may reduce N-acetylaspartic acid (NAA) concentration in the brain. Six persons with Canavan disease given lithium citrate for 60 days were reported to have reduced NAA in the basal ganglia and mild improvement in frontal white matter [Assadi et al 2010]. The clinical significance of use of lithium citrate is not known.
  • The enzyme defect in Canavan disease leads to decreased levels of acetate in the brain. In a clinical trial with glycerol triacetate in two persons with Canavan disease the compound was well tolerated; however, there was no clinical improvement [Madhavarao et al 2009]. It is speculated that higher doses of glycerol triacetate may be needed.

Animal models

  • A knockout mouse has been created, with a phenotype similar to that of human Canavan disease [Matalon et al 2000]. This model is being used to investigate pathophysiology [Surendran et al 2004] gene therapy and other modes of treatment [Matalon et al 2003].
    • Gene therapy with AAV2 was given to knockout Canavan disease mice: localized improvement did not spread to the entire brain [Matalon et al 2003].
    • Stem cell therapy in knockout Canavan disease mice was done in collaboration with Genzyme Corporation: the stem cells produced some oligodendrocytes but not enough to make myelin [Surendran et al 2004].
    • Enzyme replacement therapy using native ASPA and pegylated ASPA (i.e., ASPA in which covalent attachment of polyethylene glycol polymer chains masks the enzyme from the host allowing for longer circulation and less renal clearance) were injected into the peritoneum of Canavan disease mice. Preliminary results show that the enzyme passed the blood-brain barrier and there was a decrease of NAA in the brain. These experiments were short term; longitudinal studies are being planned [Zano et al 2011].
  • A mouse that seems to have a Canavan disease phenotype was produced by using the mutagen ethylenenitrosourea (ENU) to change the residue Gln193 to a termination codon in exon 4 (577C>T) [Traka et al 2008].

Search in the US and in Europe for information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Canavan disease is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are obligate heterozygotes; each therefore carries a single copy of a pathogenic variant in ASPA.
  • Heterozygotes are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. The phenotype is consistent within families.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. No severely affected person has been known to reproduce. Individuals with mild/juvenile Canavan disease could reproduce; this has not been reported to date.

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier (Heterozygote) Detection

Molecular genetic testing can be used to identify carriers among at-risk family members once the pathogenic variants are identified in the family.

Carrier detection using biochemical assay is not routinely possible because it relies on a complex enzyme assay in cultured skin fibroblasts.

Population Screening

Individuals of Ashkenazi Jewish heritage. Because of the relatively increased carrier rate in Ashkenazi Jews and the availability of genetic counseling and prenatal diagnosis, population screening has been initiated for Ashkenazi Jewish individuals of reproductive age in some states and is recommended in published guidelines (American College of Medical Genetics, American College of Obstetricians and Gynecologists) [ACOG Committee on Genetics 2009]. Through this type of screening program, couples in which both partners are carriers can be made aware of their status and risks before having affected children. Then, through genetic counseling and the option of prenatal testing, such families can, if they choose, bring to term only those pregnancies in which the fetus is unaffected. In population screening of people of Ashkenazi Jewish heritage, a panel of the two or three common ASPA pathogenic variants (p.Glu285Ala, p.Tyr231Ter, and p.Ala305Glu) can be expected to identify 99% of heterozygotes.

Assisted reproductive technologies. Individuals who are pursuing reproductive technologies that involve gamete (egg or sperm) donation and who are at increased risk of being heterozygous for an ASPA pathogenic variant because of family history or ethnic background should be offered screening. If the gamete recipient is a carrier, potential gamete donors can be screened to determine carrier status.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are carriers or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

Molecular genetic testing. Prenatal testing for pregnancies at 25% risk is possible by analysis of DNA extracted from fetal cells obtained by chorionic villus sampling (CVS) at approximately ten to 12 weeks' gestation or by amniocentesis usually performed at approximately 15 to 18 weeks' gestation. Both pathogenic variants present in the family must be identified before prenatal testing can be performed.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Biochemical genetic testing. For couples in which one partner is known to be a carrier and the genetic status of the other is unknown, prenatal testing can be performed by measuring the level of NAA in amniotic fluid at 15 to 18 weeks' gestation [Bennett et al 1993, Al-Dirbashi et al 2009].

Preimplantation genetic diagnosis (PGD) may be available for families in which the pathogenic variants have been identified [Yaron et al 2005].


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Canavan Foundation
    450 West End Avenue
    New York NY 10024
    Phone: 877-422-6282 (toll free); 212-873-4640
    Fax: 212-873-7892
  • National Institute of Neurological Disorders and Stroke (NINDS)
    PO Box 5801
    Bethesda MD 20824
    Phone: 800-352-9424 (toll-free); 301-496-5751; 301-468-5981 (TTY)
  • National Library of Medicine Genetics Home Reference
  • Center for Jewish Genetics
    Ben Gurion Way
    30 South Wells Street
    Chicago IL 60606
    Phone: 312-357-4718
  • National Tay-Sachs and Allied Diseases Association, Inc. (NTSAD)
    2001 Beacon Street
    Suite 204
    Boston MA 02135
    Phone: 800-906-8723 (toll-free)
    Fax: 617-277-0134
  • United Leukodystrophy Foundation (ULF)
    224 North Second Street
    Suite 2
    DeKalb IL 60115
    Phone: 800-728-5483 (toll-free); 815-748-3211
    Fax: 815-748-0844
  • Myelin Disorders Bioregistry Project

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Canavan Disease: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
ASPA17p13​.2AspartoacylaseASPA @ LOVDASPAASPA

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Canavan Disease (View All in OMIM)


Gene structure. The gene comprises 29 kb with six exons and five introns. The exons vary in size from 94 bp (exon 3) to 514 bp (exon 6). For a detailed summary of gene and protein information, see, Table A, Gene.

Pathogenic variants. See Table 2. The major pathogenic variants are p.Glu285Ala, p.Tyr231Ter, and p.Ala305Glu. (For more information, see Table A.)

Table 2.

Selected ASPA Pathogenic Variants

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​ See Quick Reference for an explanation of nomenclature.

Normal gene product. Aspartoacylase is a protein of 313 amino acids, suggesting a molecular weight of 36 kd [Kaul et al 1993]. The 93% homology of the amino acid and nucleotide sequence of human and bovine aspartoacylase suggest a high degree of conservation of this enzyme in mammals [Kaul et al 1994a]. The protein is observed in most tissues.

Recent studies have shown that ASPA is a dimer with zinc at the catalytic site analogous to other carboxypeptidases. Pathogenic variants caused conformational changes that affect the activity of the enzyme [Bitto et al 2007].

Abnormal gene product. Aspartoacylase is responsible for hydrolyzing N-acetylaspartic acid (NAA) into aspartic acid and acetate. The abnormal alleles include null variants, which make no aspartoacylase, and missense variants, which make less active forms of aspartoacylase. Although aspartoacylase is expressed widely throughout the body, its absence in the CNS leads to the specific buildup of NAA in the brain that causes demyelinization and other signs of the disease.


Published Guidelines/Consensus Statements

  • American College of Medical Genetics. Position statement on carrier testing for Canavan disease. 1998.
  • ACOG Committee on Genetics. ACOG committee opinion. Screening for Canavan disease. Number 212, November 1998. Committee on Genetics. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1999;65:91–2. [PubMed: 10390111]

Literature Cited

  • ACOG Committee on Genetics. ACOG committee opinion. Number 442, October. Prenatal and preconceptional carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol. 2009;114:950–3. [PubMed: 19888064]
  • Al-Dirbashi OY, Kurdi W, Imtiaz F, Ahmad AM, Al-Sayed M, Tulbah M, Al-Nemer M, Rashed MS. Reliable prenatal diagnosis of Canavan disease by measuring N-acetylaspartate in amniotic fluid using liquid chromatography tandem mass spectrometry. Prenat Diagn. 2009;29:477–80. [PubMed: 19235826]
  • Assadi M, Janson C, Wang DJ, Goldfarb O, Suri N, Bilaniuk L, Leone P. Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease. Eur J Paediatr Neurol. 2010;14:354–9. [PubMed: 20034825]
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  • Kurczynski TW, Victorio MC. Atypical Canavan disease associated with a p.A305E mutation and a p.P257R novel variant in the aspartoacylase gene. Abstract 312. Vancouver, Canada: American College of Medical Genetics Annual Clinical Genetics Meeting; 2011.
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  • McPhee SW, Janson CG, Li C, Samulski RJ, Camp AS, Francis J, Shera D, Lioutermann L, Feely M, Freese A, Leone P. Immune responses to AAV in a phase I study for Canavan disease. J Gene Med. 2006;8:577–88. [PubMed: 16532510]
  • Michals K, Matalon R. Canavan disease. In: Raymond GV, Eichler F, Fatemi A, Naidu S, eds. Leukodystrophies. London: Mac Keith Press, 2011:156-69.
  • Olsen TR, Tranebjaerg L, Kvittingen EA, Hagenfeldt L, Moller C, Nilssen O. Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and Swedish patients with Canavan disease. J Med Genet. 2002;39:e55. [PMC free article: PMC1735245] [PubMed: 12205125]
  • Sugarman EA, Allitto BA. Carrier testing for seven diseases common in the Ashkenazi Jewish population: implications for counseling and testing. Obstet Gynecol. 2001;97:S38–S39.
  • Surendran S, Bamforth FJ, Chan A, Tyring SK, Goodman SI, Matalon R. Mild elevation of N-acetylaspartic acid and macrocephaly: diagnostic problem. J Child Neurol. 2003;18:809–12. [PubMed: 14696913]
  • Surendran S, Shihabuddin LS, Clarke J, Taksir TV, Stewart GR, Parsons G, Yang W, Tyring SK, Michals-Matalon K, Matalon R. Mouse neural progenitor cells differentiate into oligodendrocytes in the brain of a knockout mouse model of Canavan disease. Brain Res Dev Brain Res. 2004;153:19–27. [PubMed: 15464214]
  • Tacke U, Olbrich H, Sass JO, Fekete A, Horvath J, Ziyeh S, Kleijer WJ, Rolland MO, Fisher S, Payne S, Vargiami E, Zafeiriou DI, Omran H. Possible genotype-phenotype correlations in children with mild clinical course of Canavan disease. Neuropediatrics. 2005;36:252–5. [PubMed: 16138249]
  • Traka M, Wollmann RL, Cerda SR, Dugas J, Barres BA. Nur7 is a nonsense mutation in the mouse aspartoacylase gene that causes spongy degeneration of the CNS. J Neurosci. 2008;28:11537–49. PopKo B. [PMC free article: PMC2613291] [PubMed: 18987190]
  • Yalcinkaya C, Benbir G, Salomons GS, Karaarslan E, Rolland MO, Jakobs C, van der Knaap MS. Atypical MRI findings in Canavan disease: a patient with a mild course. Neuropediatrics. 2005;36:336–9. [PubMed: 16217711]
  • Yaron Y, Schwartz T, Mey-Raz N, Amit A, Lessing JB, Malcov M. Preimplantation genetic diagnosis of Canavan disease. Fetal Diagn Ther. 2005;20:465–8. [PubMed: 16113575]
  • Zano S, Malik R, Szucs S, Matalon R, Viola RE. Modification of aspartoacylase for potential use in enzyme replacement therapy for the treatment of Canavan disease. Mol Genet Metab. 2011;102:176–80. [PMC free article: PMC3022971] [PubMed: 21095151]
  • Zeng BJ, Wang ZH, Ribeiro LA, Leone P, De Gasperi R, Kim SJ, Raghavan S, Ong E, Pastores GM, Kolodny EH. Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease. J Inherit Metab Dis. 2002;25:557–70. [PubMed: 12638939]
  • Zeng BJ, Wang ZH, Torres PA, Pastores GM, Leone P, Raghavan SS, Kolodny EH. Rapid detection of three large novel deletion of the aspartoacylase gene in non-jewish patients with Canavan disease. Mol Genet Metab. 2006;89:156–63. [PubMed: 16854607]

Suggested Reading

  • Arun P, Madhavarao CN, Moffett JR, Hamilton K, Grunberg NE, Ariyannur PS, Gahl WA, Anikster Y, Mog S, Hallows WC, Denu JM, Namboodiri AM. Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease. J Inherit Metab Dis. 2010;33:195–210. [PMC free article: PMC2877317] [PubMed: 20464498]
  • Baslow MH, Kitada K, Suckow RF, Hungund BL, Serikawa T. The effects of lithium chloride and other substances on levels of brain N-acetyl-L-aspartic acid in Canavan disease-like rats. Neurochem Res. 2002;27:403–6. [PubMed: 12064356]
  • Janson CG, Kolodny EH, Zeng BJ, Raghavan S, Pastores G, Torres P, Assadi M, McPhee S, Goldfarb O, Saslow B, Freese A, Wang DJ, Bilaniuk L, Shera D, Leone P. Mild-onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase gene. Ann Neurol. 2006;59:428–31. [PubMed: 16437572]
  • Kitada K, Akimitsu T, Shigematsu Y, Kondo A, Maihara T, Yokoi N, Kuramoto T, Sasa M, Serikawa T. Accumulation of N-acetyl-L-aspartate in the brain of the tremor rat, a mutant exhibiting absence-like seizure and spongiform degeneration in the central nervous system. J Neurochem. 2000;74:2512–9. [PubMed: 10820213]
  • Matalon R, Bhatia G, Suzucs S, Michals-Matalon K, Tyring S, Grady J. Aspartoacylase entry to the brain of Canavan mouse with hyaluronidase? J Inherit Metab. Dis. 2008;31:28.

Chapter Notes

Author History

Gita Bhatia, PhD; University of Texas Medical Branch (2009-2011)
Kimberlee Michals-Matalon, PhD, RD (2011-present)
Reuben Matalon, PhD (1999-present)

Revision History

  • 11 August 2011 (me) Comprehensive update posted live
  • 1 October 2009 (me) Comprehensive update posted live
  • 15 March 2006 (cd) Revision: deletion/duplication analysis clinically available
  • 30 December 2005 (me) Comprehensive update posted to live Web site
  • 7 November 2003 (me) Comprehensive update posted to live Web site
  • 3 October 2001 (me) Comprehensive update posted to live Web site
  • 16 September 1999 (pb) Review posted to live Web site
  • 17 April 1999 (rm) Original submission
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