Morbus Canavan
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 characterized by megalencephaly, severe mental and neurological deficits, and blindness.
Epidemiology
Canavan disease is particularly common in the Ashkenazi Jewish community . The carrier frequency among the Ashkenazi ranges from 1:37 to 1:57, with a corresponding prevalence of 1 in 6000-14000 in this high risk group. In the general population the prevalence is 1 in 100000 .
Clinical features
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 . 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 . Juvenile-onset forms may have speech difficulty, mild intellectual impairment and suffer neurological regression .
Pathology
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 . Although its effects are widespread, it has a predilection for subcortical U-fibers and Alzheimer type II astrocytes in the gray matter .
Markers
Increased levels of NAA in the urine may be detected .
Radiographic features
In Canavan disease the neuroimaging findings are diagnostic of the condition .
CT
The edematous sponginess of the white matter causes a characteristically low radiographic attenuation on CT so that it stands out from the relatively unaffected gray matter . Megalencephaly may also be also noted depending on the clinical stage .
MRI
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 :
- T1: areas of low signal
- mainly within subcortical white matter
- generally with sparing of the corpus callosum, caudate nucleus, putamen and internal capsule
- as the condition progresses atrophy of the periventricular white matter may be seen with associated ventriculomegaly
- globi pallidi and thalami are usually affected as well
- T2/FLAIR: findings as above except for areas of high signal in the affected white matter
- DWI: restricted diffusion within the diseased white matter
- MR spectroscopy: markedly elevated NAA and NAA:creatine ratio are pathognomonic for the condition .
- this can be remembered using the mnemonic CaNAAvan
There is no enhancement of affected regions on either CT or MRI .
Treatment and prognosis
The condition is fatal with death resulting at 2-5 years and treatment is generally supportive . No effective treatment is yet available . However, genetic therapies are being trialled and seem to reduce the level of NAA within the brain .
History and etymology
It was first described by Myrtelle Canavan (1879-1953), an American neuropathologist, in her 1931 seminal paper .
Differential diagnosis
Consider other dysmyelinating diseases such as:
- Alexander disease: anterior dominance, diffuse late in disease course, normal NAA on MRS
- Pelizaeus-Merzbacher disease: associated with cerebellar atrophy, has a tigroid pattern of hyperintensity, spares subcortical U-fibers
- adrenoleukodystrophy: spares subcortical U-fibers, has a characteristic occipitoparietal periventricular white matter distribution
- metachromatic leukodystrophy: spares subcortical U-fibers, has a characteristic 'butterfly' pattern
Siehe auch:
- Morbus Alexander
- adrenoleukodystrophy
- Metachromatische Leukodystrophie
- Pelizaeus Merzbacher disease
- dysmyelinating disease
und weiter:
Assoziationen und Differentialdiagnosen zu Morbus Canavan:
