Christianson syndrome (CS) is an X-linked monogenic neurodevelopmental/neurodegenerative disorder arising from loss of function mutations in the endosomal pH regulator, Na+, K+/H+ exchanger isoform 6 (NHE6) and is estimated to afflict 1 in 16,000–100,000 people worldwide. In addition to significant limitations in cognitive and adaptive abilities, all affected males have ataxia. Mitochondrial dysfunction is increasingly being recognized as an important factor contributing to the pathogenesis of ataxia. In particular, dysregulated mitochondrial fusion and fission events can now be regarded as playing important pathogenic roles in neurodegeneration. In CS, Purkinje cells (PCs) are more vulnerable to cell death in the anterior cerebellum than those in the posterior. As anterior PCs fire spontaneous action potentials at a higher frequency than those in the posterior thereby requiring a higher energy demand, we wanted to test for changes in mitochondria. We hypothesised that the anterior PCs are more sensitive to ATP depletion due to dysregulation of mitochondria making them more susceptible to cell death. Using RNA sequencing and DESeq2 analysis on the anterior and posterior cerebellum of wildtype and CS mice at disease onset, we identified multiple gene families regulating mitochondria that were highly dysregulated in the anterior cerebellum, particularly those regulating fission and fusion. We found Dynamin-related protein 1 and Optic atrophy type 1, important regulators of fission and fusion respectively, were downregulated exclusively in the anterior cerebellum of CS mice. Our findings suggest that mitochondrial dysfunction may contribute to the anterior PC vulnerability seen in CS.