Cerebellar ataxia with normal intelligence in an adult patient with PEX10 mutation

Background: Cerebellar ataxia is a common clinical sign caused by dysfunction of the complex circuitry connecting the basal ganglia, cerebellum and cerebral cortex. The many causes of cerebellar ataxia include inflammatory diseases, genetic conditions and acquired and inherited metabolic disorders (IEM), suchc as aminoacidopathies, peroxisomal and lysosomal storage disorders, congenital glycosylation disorders, organic acidosis, and mitochondrial diseases. In the context of IEM, cerebellar ataxias are often associated with developmental regression, intellectual disability, seizures, or tone abnormalities. We describe an adult patient with progressive ataxia and normal intelligence, caused by a homozygous pathogenic variant in PEX10 gene.

Case report: We report the case of a 31-year-old female with normal intelligence and slowly progressive truncal ataxia evident from 6 years. Clinical examination and neuroimaging studies confirmed cerebellar atrophy. The patient lost ambulation at 28 years, and also complained on frequent headaches and fatigue.

Rresults: Whole exome sequencing (WES) revealed a homozygous pathogenic variant c.1A>G p.(Met1?) in PAX10, causing the loss of the start codon. Patient was prescribed a diet low in phytanic acid and omega 3.

Discussion: We reported an unusual case of slowly progressive cerebellar ataxia in a patient with normal intelligence, caused by pathogenic variant in PEX10. More than 30 different mutations have been identified in the PEX10, and genotype-phenotype correlation studies have shown that missense mutations are associated with milder phenotype, which possibly explains the spectrum seen in our patient including normal intelligence. In conclusion, IEMs, including peroxisomal disorders, should be considered in the differential diagnosis of cerebellar ataxia. Early diagnosis is of crucial importance for both diagnostic and therapeutic purposes, as many neurometabolic disorders are fully or partially treatable.