*5.3.4 Ataxia with vitamin E deficiency*

Ataxia with vitamin E deficiency (AVED) is caused by variants in the APTT gene, which encodes the synthesis of the alpha-tocopherol transfer protein, responsible for incorporating vitamin E into very low-density proteins in the liver, which will transport it to the brain. The first manifestations are observed between 4 and 18 years of age in individuals with or without a history of malabsorption disorders [66]. Subjects with AVED develop a neurological phenotype very similar to Friedreich's ataxia [67]. AVED is characterised by progressive ataxia, areflexia, head tremor, loss of proprioception and retinitis pigmentosa [68]. Supplementation improves symptoms and prevents the progression of the disease [68].

### *5.3.5 Autosomal-recessive spastic ataxia of Charlevoix: Saguenay*

Autosomal-recessive spastics ataxia of Charlevoix Saguenay (ARSACS) is caused by mutations in the SACS gene which is located on chromosome 13q12.12 [69]. SACS gene encodes sacsin, a protein that has chaperone activity and interacts with the proteasome, but is also involved in mitochondrial function and affects axonal and dendritic transport [70]. The mean age at onset is approximately 6 years (range: 0–40 years) [71]. ARSACS is clinically characterised by early-onset progressive cerebellar ataxia, spasticity and peripheral neuropathy. Oculomotor disturbances and dysarthria are also common manifestations. A characteristic finding is the presence of yellow streaks of hypermyelinated fibres radiating from the edges of the optic disc seen on ophthalmologic examination. In the optical coherence tomography study, an increase in the thickness of the retinal fibre layer can be observed [72]. MRI imaging shows atrophy of the cerebellar vermis, atrophy of the posterior part of the corpus callosum, and linear hypointensities in the pons on T2 and T2-FLAIR [73].
