A progressive leukodystrophy caused by spongy
degeneration of the central nervous system. The clinical triad of hypotonia,
macrocephaly, and lack of head control in an infant more than 3 to 5 months
old is suspicious for this disorder.
Canavan-Van Bogaert-Bertrand Disease; Canavan Sclerosis;
Van-Bogaert-Bertrand Syndrome; Van-Bogaert-Bertrand Spongy Degeneration
Syndrome; Cerebral White Matter Spongy Degeneration; Spongy Degeneration of
the Nervous System; Familial Spongy Degeneration; Encephalopathia
Spongiotica; Acetylaspartic Aciduria; Progressive Degenerative Subcortical
Encephalopathy; Aminoacylase-2 Deficiency; ACY2 Deficiency; Aspartoacylase
Although the disorder has been described in all ethnic
groups, the highest incidence has been reported in Ashkenazi Jews, in whom
it occurs in approximately 1:13,000 live births.
Autosomal recessive. The disease is caused by
mutations of the aspartoacylase gene, which has been mapped to 17pter-p13.
Aspartoacylase deficiency leads to a buildup of
N-acetylaspartate. This defect results in demyelination of the white matter
of the internal and external capsule, corpus callosum, subcortical white
matter, and posterior fossa.
It is based on clinical features and the demonstration of
significantly elevated N-acetylaspartate levels in urine, blood,
cerebrospinal fluid, and the brain (detected by magnetic resonance
spectroscopy). Neuroradiologic studies show white matter degeneration in
affected areas. Brain histology shows spongy degeneration (unspecific), but
is usually not required for the diagnosis. Electron microscopy reveals
swelling of the astrocytes and abnormalities of the mitochondria. Cultured
skin fibroblasts show reduced aspartoacylase activity.
Three different forms of Canavan disease (CD)
have been described (neonatal, infantile, and late-onset form). The
infantile form seems to be the most common form, and only the rate of disease
progression is highly variable. Onset is usually in early infancy at 2
to 4 months of age with loss of the already acquired milestones, while death
occurs most often within the first decade of life (although death by
approximately 18 months of age is not uncommon). However, survival into the
teens has also been reported, and one patient survived for more than 30 years.
Patients initially present with poor head control due to hypotonia or atonia
of the neck muscles. Hypotonia soon becomes generalized and changes to
spastic diplegia or quadriplegia as the disease progresses, ending in late
decerebrate or decorticate posturing. Generalized seizures are common.
Ocular features include optic atrophy, nystagmus, and finally blindness.
Closure of the anterior fontanelle is delayed, and macrocephaly is a common
finding. Patients usually are deaf. Copious oral secretions and
gastroesophageal reflux can occur. No effective treatment is available.
Therapies are mainly symptomatic (e.g., seizure control, physiotherapy).
Gene therapies are currently under investigation.
The patient's seizure control should
be assessed and medications altered, if necessary. A chest radiograph is
recommended if recurrent or recent aspiration is an issue. Consider
premedication with a nonparticulate antacid, H2-antagonist, or proton
pump inhibitor. Avoid antidopaminergic medications because they can
exacerbate existing extrapyramidal movement disorders. Sedative and
anxiolytic premedication and the presence of the primary caregiver during
induction of ...