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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Neurology

Understanding the Basics of Canavan Disease

At a Glance

Canavan disease is a rare, inherited genetic disorder that damages the brain's white matter. It is caused by mutations in the ASPA gene, which leads to a toxic buildup of NAA in the brain. The most common infantile form causes an unusually large head, weak muscle tone, and developmental delays.

Receiving a diagnosis of Canavan disease is a life-altering moment that often comes after a period of deep uncertainty. It is natural to feel overwhelmed, but please know that you are not alone, and this diagnosis is not the result of anything you did or did not do. Canavan disease is a genetic condition that you and your partner both happened to carry silently [1]. Understanding the mechanics of the disease is the first step in moving from a place of shock to a place of informed advocacy for your child.

What is Canavan Disease?

Canavan disease is a rare, inherited neurological disorder that belongs to a group of conditions called leukodystrophies [2]. These are diseases that affect the white matter of the brain—the “insulation” on the brain’s wiring that allows signals to travel quickly and efficiently [3].

In a child with Canavan disease, this insulation, known as myelin, does not form correctly or begins to break down [4][5]. This leads to “spongy” changes in the brain tissue, which interferes with the brain’s ability to send and receive messages to the rest of the body [6][7].

The Role of the ASPA Gene and NAA

The root cause of this condition is a change (mutation) in the ASPA gene [1][8]. This gene is responsible for producing an enzyme called aspartoacylase [9].

  • The Normal Process: In a typical brain, this enzyme breaks down a substance called N-acetylaspartic acid (NAA) [10].
  • What Happens in Canavan Disease: Because the enzyme is missing or doesn’t work correctly, NAA builds up to high levels in the brain [9][6].
  • The Result: This excess NAA is toxic to the brain’s white matter. It causes fluid-filled spaces (vacuoles) to form, leading to the “spongy” degeneration that characterizes the disease [6][11].

Understanding the Forms of the Disease

Canavan disease is typically classified into two main forms based on when symptoms begin and their severity:

  1. Neonatal/Infantile Form: This is the most common and severe version [2]. Symptoms usually appear between 3 and 6 months of age and include macrocephaly (an unusually large head), weak muscle tone (hypotonia), and delays in reaching developmental milestones like sitting or head control [2][12].
  2. Mild/Juvenile Form: This is much rarer. Children with this form may have only mild delays in speech or motor skills, and the condition may not be diagnosed until later in childhood [13][14].

Why Did This Happen?

Canavan disease is an autosomal recessive condition [1]. This means that for a child to be affected, they must inherit two copies of the mutated gene—one from each parent [1].

Parents of children with Canavan disease are typically “carriers.” Carriers have one healthy gene and one mutated gene; they do not have the disease themselves and often have no idea they carry the mutation until they have an affected child [3]. It is a random genetic event, and there is no way you could have prevented it through lifestyle choices or actions during pregnancy.

Who is Affected?

While Canavan disease is found in people of all ethnic backgrounds and is considered a pan-ethnic disorder, it is significantly more common in certain populations [15][12].

Population Group Estimated Carrier Frequency Estimated Disease Incidence
Ashkenazi Jewish ~ 1 in 40 1 in 6,400 to 13,500 [3]
General Population Significantly lower Extremely rare [16]

Recent advances in genetic testing, such as Next-Generation Sequencing (NGS), have made it easier to diagnose the condition in diverse populations where the specific gene mutations may differ from those most commonly seen in the Ashkenazi Jewish community [3][17]. This information is a tool that allows you to better understand your child’s needs and connect with the right specialists for their care.

Common questions in this guide

What causes Canavan disease?
Canavan disease is caused by a mutation in the ASPA gene, which normally produces an enzyme needed to break down NAA in the brain. Without this working enzyme, toxic levels of NAA build up and damage the brain's white matter.
What are the different forms of Canavan disease?
There are two main forms: the severe infantile form and the rare mild juvenile form. The infantile form is more common, with symptoms like weak muscle tone, developmental delays, and an unusually large head appearing between 3 and 6 months of age.
Can Canavan disease be prevented?
Because it is an inherited genetic condition, it cannot be prevented through lifestyle choices during pregnancy. It occurs randomly when a child inherits two copies of the mutated gene from parents who are silent carriers.
How does the ASPA gene mutation affect the brain?
The mutation prevents the body from making an enzyme that regulates a substance called NAA. The resulting buildup of excess NAA is toxic, destroying the brain's protective myelin and causing fluid-filled spaces to form in the brain tissue.
Should my family get genetic testing for Canavan disease?
If you have a child diagnosed with Canavan disease, your doctor may recommend carrier screening and genetic testing for your other children or extended family members. This helps identify if others are silent carriers of the ASPA gene mutation.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which specific form of Canavan disease does my child have: the infantile/severe form or the mild/juvenile form?
  2. 2.Can you explain my child's specific ASPA gene mutations and what they mean for the enzyme activity level?
  3. 3.What are the next steps for identifying a care team, including a pediatric neurologist and a metabolic specialist?
  4. 4.Are there clinical trials or research studies currently recruiting for Canavan disease that we should consider?
  5. 5.Should our other children or extended family members undergo genetic testing or carrier screening?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
  1. 1

    Severe retinal degeneration in a patient with Canavan disease.

    Benson MD, Plemel DJA, Freund PR, et al.

    Ophthalmic genetics 2021; (42(1)):75-78 doi:10.1080/13816810.2020.1827441.

    PMID: 32975148
  2. 2

    Canavan's spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature.

    Rossler L, Lemburg S, Weitkämper A, et al.

    Journal of ultrasound 2023; (26(4)):757-764 doi:10.1007/s40477-022-00667-2.

    PMID: 35187608
  3. 3

    Canavan Disease: Clinical and Laboratory Profile from Southern Part of India.

    Gowda VK, Bharathi NK, Bettaiah J, et al.

    Annals of Indian Academy of Neurology 2021; (24(3)):347-350 doi:10.4103/aian.AIAN_386_20.

    PMID: 34446995
  4. 4

    Increasing N-acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the CNS Pathologies of Canavan Disease.

    Appu AP, Moffett JR, Arun P, et al.

    Frontiers in molecular neuroscience 2017; (10()):161 doi:10.3389/fnmol.2017.00161.

    PMID: 28626388
  5. 5

    Renewal of oligodendrocyte lineage reverses dysmyelination and CNS neurodegeneration through corrected N-acetylaspartate metabolism.

    Lotun A, Li D, Xu H, et al.

    Progress in neurobiology 2023; (226()):102460 doi:10.1016/j.pneurobio.2023.102460.

    PMID: 37149081
  6. 6

    Ablating the Transporter Sodium-Dependent Dicarboxylate Transporter 3 Prevents Leukodystrophy in Canavan Disease Mice.

    Wang Y, Hull V, Sternbach S, et al.

    Annals of neurology 2021; (90(5)):845-850 doi:10.1002/ana.26211.

    PMID: 34498299
  7. 7

    rAAV Gene Therapy in a Canavan's Disease Mouse Model Reveals Immune Impairments and an Extended Pathology Beyond the Central Nervous System.

    Ahmed SS, Schattgen SA, Frakes AE, et al.

    Molecular therapy : the journal of the American Society of Gene Therapy 2016; (24(6)):1030-1041 doi:10.1038/mt.2016.68.

    PMID: 27039844
  8. 8

    Cribriform Appearance of White Matter in Canavan Disease Associated with Novel Mutations of ASPA Gene.

    Bhat MD, Manjunath N, Kumari R, et al.

    Journal of pediatric genetics 2022; (11(4)):267-271 doi:10.1055/s-0041-1725118.

    PMID: 36267868
  9. 9

    Development of bisubstrate analog inhibitors of aspartate N-acetyltransferase, a critical brain enzyme.

    Mutthamsetty V, Dahal GP, Wang Q, Viola RE

    Chemical biology & drug design 2020; (95(1)):48-57 doi:10.1111/cbdd.13586.

    PMID: 31260162
  10. 10

    Astroglial conditional Slc13a3 knockout is therapeutic in murine Canavan leukodystrophy.

    Hull VL, Wang Y, McDonough J, et al.

    Annals of clinical and translational neurology 2024; (11(4)):1059-1062 doi:10.1002/acn3.52010.

    PMID: 38282243
  11. 11

    Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice.

    Hull V, Wang Y, Burns T, et al.

    Annals of neurology 2020; (87(3)):480-485 doi:10.1002/ana.25674.

    PMID: 31925837
  12. 12

    The natural history of Canavan disease: 23 new cases and comparison with patients from literature.

    Bley A, Denecke J, Kohlschütter A, et al.

    Orphanet journal of rare diseases 2021; (16(1)):227 doi:10.1186/s13023-020-01659-3.

    PMID: 34011350
  13. 13

    A case of juvenile Canavan disease with distinct pons involvement.

    Çakar NE, Aksu Uzunhan T

    Brain & development 2020; (42(2)):222-225 doi:10.1016/j.braindev.2019.11.009.

    PMID: 31839386
  14. 14

    Clustering of Juvenile Canavan disease in an Indian community due to population bottleneck and isolation: genomic signatures of a founder event.

    Kotambail A, Selvam P, Muthusamy K, et al.

    European journal of human genetics : EJHG 2023; (31(1)):73-80 doi:10.1038/s41431-022-01198-4.

    PMID: 36202930
  15. 15

    Canavan disease: an Arab scenario.

    Zayed H

    Gene 2015; (560(1)):9-14.

    PMID: 25668701
  16. 16

    Novel mutation in an Egyptian patient with infantile Canavan disease.

    Zaki OK, El Abd HS, Mohamed SA, Zayed H

    Metabolic brain disease 2016; (31(3)):573-7 doi:10.1007/s11011-015-9772-z.

    PMID: 26613958
  17. 17

    NGS-based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results - a pilot study.

    Singh K, Bijarnia-Mahay S, Ramprasad VL, et al.

    BMC medical genetics 2020; (21(1)):216 doi:10.1186/s12881-020-01153-4.

    PMID: 33138774

This page provides general information about the basics of Canavan disease for educational purposes. Always consult your pediatric neurologist, metabolic specialist, or genetic counselor for medical advice specific to your child's diagnosis and care.

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