Clinical features of four unrelated Japanese patients with autosomal recessive spinocerebellar ataxia type 32

Peroxiredoxin 3 (PRDX3) encodes a mitochondrially localized antioxidant enzyme. Biallelic pathogenic variants in PRDX3 cause autosomal recessive spinocerebellar ataxia type 32 (SCAR32), a rare form of spinocerebellar ataxia. We report four unrelated Japanese patients with SCAR32 identified among 411 ataxia cases negative for repeat expansion disorders. Age at onset was 9-30 years, with a predominantly pure cerebellar phenotype; one patient had autoimmune comorbidities. MRI showed cerebellar atrophy and T2 hyperintensity in dentate nuclei in all patients, and three had cerebellar cortical T2 hyperintensity, a potentially representative feature of SCAR32. Genetic analysis identified one homozygous and three compound heterozygous PRDX3 nonsense variants: the previously reported p.Arg207* in all patients, p.Arg170* in two, and novel p.Gln50* in one. The relatively high p.Arg207* allele frequency in East Asians and the 0.97% prevalence in our undiagnosed ataxia cohort support SCAR32 as an important cause of early-onset autosomal recessive cerebellar ataxia in Japan.