Portneuf Spastic Ataxia is classified as an autosomal recessive spastic ataxia with leukoencephalopathy (ARSAL); it is caused by homozygous or compound heterozygous complex genomic rearrangements involving the MARS2 gene on chromosome 2q33. Most patients, however not all, have a genetic link to the Portneuf County of Quebec, and some analyses suggest that one common mutation may be responsible for 97% of the carrier chromosomes in Quebec.
Although there is complete penetrance, there is a wide intra- and interfamilial variability in expression of the phenotype. The age of onset varies from birth to 60 years, depending on the severity, but all patients present with ataxia, spasticity and hyperreflexia. Other clinical features include urinary urgency, ataxic and spastic dysarthria, dystonic positioning, mild horizontal nystagmus, scoliosis, optic atrophy with cataracts in older patients, mild hearing impairment, and mild cognitive impairment.
On MRI, cerebellar atrophy, cortical atrophy and leukoencephalopathy are the classic findings. patients will have mild to severe cerebellar atrophy typically involving the vermis and the cerebellar hemispheres proportionally, although not always. Mild to moderate cerebral atrophy may be present as well in the frontoparietal or parieto-occipital areas. Non-specific white matter changes on T2 -weighted and FLAIR sequences on brain MRI may be a later finding that can range from diffuse periventricular changes on T2 imaging, to mild localized changes in the periventricular, juxtacortical or deep white matter.
References:
I. Bayat V, Thiffault I, Jaiswal M, Tétreault M, Donti T, Sasarman F, et al. (2012) Mutations in the Mitochondrial Methionyl-tRNA Synthetase Cause a Neurodegenerative Phenotype in Flies and a Recessive Ataxia (ARSAL) in Humans. PLoS Biol 10(3): e1001288. https://doi.org/10.1371/journal.pbio.1001288
II. Thiffault, M. F. Rioux, M. Tetreault, J. Jarry, L. Loiselle, J. Poirier, F. Gros-Louis, J. Mathieu, M. Vanasse, G. A. Rouleau, J. P. Bouchard, J. Lesage, B. Brais; A new autosomal recessive spastic ataxia associated with frequent white matter changes maps to 2q33–34, Brain, Volume 129, Issue 9, 1 September 2006, Pages 2332-2340, https://doi.org/10.1093/brain/awl110