Canavans Syndrome

Canavan's syndrome (see Ta.b.!e..3.0.:6 ) is a spongy degeneration of the CNS with abnormalities found particularly in the white matter. Vacuoles accumulate in a variety of brain cells, particularly astrocytes, and produce the spongy appearance. The vacuoles result from excessive fluid accumulation, apparently from metabolic disturbances that produce

dysmyelination.y The precise cause of these abnormalities remains uncertain. Recent suggestions include a metabolic error in the W-acetylaspartate signal as a result of an aspartoacylase defect.y There are increased levels of W-acetylaspartic acid in the urine and plasma and aspartoacylase deficiencies in cultured skin fibroblasts.[64] In addition, astrocytes have abnormal mitochondria with reduced levels of adenosine triphosphate. The brain in Canavan's syndrome has an increased water content and decreased lipids. Chemical changes are limited to the white matter, notably myelin, and are nonspecific. Demyelination is extensive, but axonal fibers and the oligodendroglia are not extensively affected.

The infantile form appears to be inherited as an autosomal recessive disorder. This disease occurs predominantly in Jewish individuals of northeastern European heritage and in Saudi Arabians. y The neonatal and juvenile forms appear to be sporadic.

The three types of Canavan's syndrome all are marked by spongiform leukoencephalopathy, but the age of presentation distinguishes them (see TableSGdS ). The infantile form, or classic Canavan's syndrome, begins within a few months of birth, and death generally occurs by 3 to 4 years of age. The infant initially is hypotonic and has poor head and neck control. Megencephalopathy is common, and arrested development is consistent. In the second 6 months, hypotonia is replaced by spasticity^ and often by decorticate and decerebrate posturing. Some hyperreactivity is precipitated by auditory, visual, and tactile stimuli. Vision deteriorates as optic atrophy and nystagmus develop. Seizures of various types, including focal and myoclonic seizures, are usual, and choreoathetotic or dystonic movements can occur. Dysautonomia in the form of paroxysmal episodes of sweating, hyperthermia, vomiting, and hypotension are terminal manifestations.

The neonatal form of Canavan's syndrome is deadly within a few weeks and is characterized by lethargy, hypotonia, diminished spontaneous movement, and difficulty in swallowing. The rare juvenile form develops after 5 years of age and extends into adolescence. Ataxia, tremor, ptosis, and mental deterioration are characteristic. The course is characterized by progressive cerebellar symptoms, dysarthria, dementia, spasticity, and loss of vision. Other organ systems are sometimes involved, resulting in diabetes mellitus, hyperaldosteronism, and heart block, but there is no correlation between the severity of the morphological white matter changes and the clinical presentation. y There is still no specific curative therapy for Canavan's disease, and symptomatic support includes nutritional therapy and generous use of antiepileptic drugs and antibiotics. Whereas currently the prognosis is poor, future research efforts utilizing cloistered populations with the disease, such as those found in Saudi Arabia, may lead to new discoveries.

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