Canavan disease: a review of recent developments.

The clinical features, causes and potential treatment of Canavan disease are reviewed. The course of the illness can show considerable variation, and can sometimes be protracted. It has an autosomal recessive mode of inheritance, and is caused by mutations in the gene for aspartoacetylase, localized to the short arm of chromosome 17. The changes in the central nervous system are related to the deficiency of aspartoacyclase which leads to an excess of N-acetylaspartate. Prenatal diagnosis of Canavan disease is possible by the measurement of N-acetylaspartate in the amniotic fluid, but the method of choice is by DNA analysis. If an infant is suspected of having the disease, due to megalencephaly and clinical deterioration, the diagnosis can be confirmed by elevated N-acetylaspartate levels in the urine, blood, and spinal fluid--and in the brain using proton magnetic resonance spectroscopy. Neuroradiological investigations confirm the white matter degeneration. Reports of children with megalencephaly, and similar clinical findings, but with normal metabolic tests, are also considered. Until recently treatment was symptomatic, such as the control of seizures, but now there is a possibility though not yet proven, of using gene therapy with modification of the phenotype of brain cells while bypassing the blood-brain barrier and the ependyma. This seems to be well tolerated, and was associated with biochemical, radiological, and clinical changes. The development of knockout mice for Canavan disease should help in the development of gene transfer vectors to treat Canavan disease and for understanding the pathophysiology.