Canavan disease

Dr Craig Hacking and A.Prof Frank Gaillard et al.

Canavan disease, also known as spongiform degeneration of white matter (not to be confused with Creutzfeldt-Jakob Disease) or aspartoacylase deficiency, is a leukodystrophy clinically characterised by megalencephaly, severe mental and neurological deficits, and blindness. 

Canavan disease is particularly common in the Ashkenazi Jewish community 1. The carrier frequency among the Ashkenazi ranges from 1:37 to 1:57, with a corresponding prevalence of 1 in 6000-14000 1.

There are a wide range of clinical features, but generally there is a progression from lethargy and hypotonia, to macrocephaly (due to underlying megalencephaly) and spasticity, to blindness and seizures, to decerebrate posturing and eventual death 2. In the vast majority of patients, clinical onset is in infancy with death before 5 years of age, and often before 18 months, but juvenile-onset forms of the disease have also been reported 2

It is an autosomal recessive disorder due to a gene mutation on the short arm of chromosome 17 leading to deficiency of N-acetylaspartoacylase, a key enzyme in myelin synthesis, with resultant accumulation of N-acetylaspartate (NAA) in the brain, cerebrospinal fluid, plasma, and urine 3,4. Although its effects are widespread, it has a predilection for subcortical U-fibers and Alzheimer type II astrocytes in the gray matter 3,5.

The oedematous sponginess of the white matter causes a characteristically low radiographic attenuation on CT so that it stands out from the relatively unaffected gray matter 4. Megalencephaly may also be also noted depending on the clinical stage 4

MRI confirms the megalencephalic appearance and provides more detail of the white matter disease, which is typically diffuse, bilateral, and involving the subcortical U-fibers 4-8:

  • T1: low signal in white matter
  • T2: high signal in white matter
  • MR spectroscopy: markedly elevated NAA and NAA:creatine ratio
    • this can be remembered using the mnemonic CaNAAvan

There is no enhancement of affected regions on either CT or MRI 5-8.

The condition is fatal with death resulting at 2-5 years and treatment is generally supportive 4. No effective treatment is yet available 4.

It was first described by Myrtelle Canavan (1879-1953), an American neuropathologist, in her 1931 seminal paper 9,10

Consider other dysmyelinating diseases such as:

Inborn errors of metabolism
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Article information

rID: 1045
Tags: cases, cases
Synonyms or Alternate Spellings:
  • Canavan's disease
  • Spongiform degeneration of white matter
  • Spongy degeneration of the brain
  • Aspartoacylase deficiency

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    Case 1: MR spectroscopy
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    Case 2: probable
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    Case 3: probable
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