Juvenile Canavan Disease presenting with intention tremor: a second case report

Background: Canavan disease is a rare neurodegenerative leukodystrophy due to biallelic variants in ASPA. The classical presentation is in infancy with macrocephaly, hypotonia, developmental delay and spasticity. Congenital and juvenile presentations are less common. Magnetic resonance imaging (MRI) scans of the brain in infantile Canavan disease typically show spongiform degeneration of the white matter.

Case Study: We describe a second case of juvenile Canavan disease presenting with intention tremor. The proband presented at 13 years of age with a 5-year history of tremor and incoordination. She attends a mainstream school, and has consanguineous parents of Pakistani ethnicity. An MRI scan of her brain showed increased signal in the basal ganglia consistent with a possible diagnosis of mitochondrial disease.

Results: Her urine organic acids showed a mildly increased peak of N-acetylaspartic acid (NAA), and she was found to have homozygous likely pathogenic c.820G>A p.(Gly274Arg) variants in ASPA. A review of her MRI brain at our centre confirmed the basal ganglia changes, but also identified subtle white matter signal abnormalities.

Discussion: The c.820G>A p.(Gly274Arg) variant in ASPA has been widely reported with significant clinical heterogeneity. In 2019 a Turkish patient with the same homozygous missense variants was reported after presenting with tremor. This patient had basal ganglia and pons signal changes without obvious white matter involvement. We recommend consideration of juvenile Canavan disease and testing of urine organic acids in individuals presenting with intention tremor with MRI brain changes.