Disease Profile

Canavan disease

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of Onset

Infancy

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ICD-10

E75.2

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

Canavan-van Bogaert-Bertrand disease; Spongy degeneration of the central nervous system; Von Bogaert-Bertrand disease;

Categories

Congenital and Genetic Diseases

Summary

Canavan disease is a progressive, fatal, genetic disorder affecting the central nervous system, muscles, and eyes. Early symptoms in infancy may include increased head size, weakness, low muscle tone and loss of head control. Symptoms progress to seizures, blindness, inability to move voluntarily and difficulty eating solids or swallowing liquids. This condition is caused by changes in the ASPA gene and is inherited in an autosomal recessive pattern. Canavan disease is diagnosed based on symptoms, laboratory testing, and genetic testing. There is no specific treatment. Treatment is focused on managing symptoms.[1][2][3][4]

Symptoms

The following list includes the most common signs and symptoms in people with Canavan disease (CD). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list also does not include every symptom or feature that has been described in Canavan disease.[4][2][3]

  • Damage to the optic nerve (Optic atrophy)
  • Blindness
  • Deafness (Hearing loss)
  • Increased head size (macrocephaly)
  • Intellectual disability and developmental delay
  • Low muscle tone (hypotonia)
  • Gastroesophageal reflux
  • Feeding difficulties in infancy
  • Inability to straighten joints (Flexion contractures)
  • Difficulty holding up head when pulled into a seated position (Head lag)
  • Abnormal growth of white matter in the brain (leukodystrophy)
  • Sleep disturbances

Infants with Canavan disease appear normal at birth and usually develop symptoms between two and six months of age. These include low muscle tone, poor head control, an increased head size, and poor motor development. Later symptoms include optic nerve damage, blindness, and seizures. Over time, stiffening of arms and legs combined with low muscle tone, lead to an inability to move and swallow voluntarily.[3][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
EEG abnormality
0002353
Feeding difficulties in infancy
0008872
Global developmental delay
0001263
Optic atrophy
0000648
Reduced consciousness/confusion
Disturbances of consciousness
Lowered consciousness

[ more ]

0004372
30%-79% of people have these symptoms
Abnormality of visual evoked potentials
0000649
Blindness
0000618
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hypertonia
0001276
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Muscular hypotonia
Low or weak muscle tone
0001252
5%-29% of people have these symptoms
Abnormality of retinal pigmentation
0007703
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Flexion contracture
Flexed joint that cannot be straightened
0001371
Seizure
0001250
Percent of people who have these symptoms is not available through HPO
Aplasia/Hypoplasia involving the central nervous system
Absent/underdeveloped central nervous system tissue
0002977
Autosomal recessive inheritance
0000007
Brain atrophy
Brain degeneration
Brain wasting

[ more ]

0012444
CNS demyelination
0007305
Delayed closure of the anterior fontanelle
Later than typical closing of soft spot of skull
0001476
Elevated urinary N-acetylaspartic acid level
0032272
Generalized-onset seizure
0002197
Increased circulating N-Acetylaspartic acid concentration
0032273
Increased CSF N-Acetylaspartic acid concentration
0032274
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Opisthotonus
0002179

Cause

Canavan disease is caused by genetic alterations in the ASPA gene.[2][4]

Diagnosis

Canavan disease is diagnosed based on the symptoms, laboratory results showing elevated levels of N-acetylaspartic acid (NAA) in urine, and genetic testing confirming genetic changes in the ASPA gene.[2][4]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    There is no specific treatment for Canavan disease. Treatment is aimed at preventing and/or managing the known symptoms and complications associated with this condition. This may include seizure medication, physical and other therapies, and maintenance of food and water intake.[1][2][4]

    Specialists who might be involved the care of someone with Canavan disease include:

    • Neurologist
    • Ophthalmologist (eye doctor)
    • Genetics specialist (genetic counselor and/or geneticist)
    • Physical therapist
    • Gastroenterologist

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn More

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Canavan disease. This website is maintained by the National Library of Medicine.
      • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Canavan disease. Click on the link to view a sample search on this topic.

          References

          1. Roscoe RB, Elliott C, Zarros A, Baillie GS. Non-genetic therapeutic approaches to Canavan disease.. J Neurol Sci. Jul 15, 2016; 366:116-124. https://www.ncbi.nlm.nih.gov/pubmed/27288788.
          2. Hoshino H, Kubota M. Canavan disease: clinical features and recent advances in research. Pediatr Int. Aug 2014; 56(4):477-83. https://www.ncbi.nlm.nih.gov/pubmed/24977939.
          3. Bokhari MR, Samanta D, Bokhari SRA. Canavan Disease. StatPearls. Updated Feb 21, 2020; www.ncbi.nlm.nih.gov/books/NBK430816.
          4. Matalon R, Delgado L, Michals-Matalon K. Canavan Disease. GeneReviews. Updated Sept 13, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1234/.
          5. Kronn D, Oddoux C, Phillips J, Ostrer H. Prevalence of Canavan disease heterozygotes in the New York metropolitan Ashkenazi Jewish population.. Am J Hum Genet. 1995; 57(5):1250-1252. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1801394/.
          6. Feigenbaum A, Moore R, Clarke J, et al. Canavan disease: carrier-frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay.. AM J Med Genet A. 2004; 124A:142-147. https://www.ncbi.nlm.nih.gov/pubmed/14699612.