We read with interest the article by Inbar-Feigenberg about two siblings carrying the same POLG1 mutations inherited from their consanguineous parents. Both siblings presented with cerebellar atrophy (Inbar-Feigenberg et al. 2018). We have the following comments and concerns. Cerebellar atrophy is a common CNS manifestation of mitochondrial disorders (MIDs) and has been reported in specific and non-specific MIDs. Specific MIDs associated with cerebellar atrophy include MELAS, MERRF, Leigh syndrome, MIDD, NARP, CPEO and CPEO plus, KSS, LHON, IOSCA, PCH6, ADOA, and DIDMOAD (Table 1). In nonspecific MIDs cerebellar atrophy was reported in patients carrying mutations in the RARS2, SLC25A46, CoQ10, and EXOSC3 genes respectively (Bindu et al. 2015). Mutations in the POLG1 gene have been also repeatedly reported in association with cerebellar atrophy (Mehta et al. 2011). Cerebellar atrophy may go along with or without clinical manifestations.

The authors mention a stroke-like lesion (SLL), the morphological equivalent of a stroke-like episode (SLE) in the cerebellum of patients carrying POLG1 mutations (Inbar-Feigenberg et al. 2018). However, SLLs typically occur supratentorially and are characterised by DWI and ADC hyperintensities. When searching Pubmed for cerebellar SLLs, no hit could be achieved. Thus, it would be interesting to know if the authors have ever observed a cerebellar SLL in their MID cohort. Which were the clinical manifestations of the cerebellar SLE, were NO-precursors given, did they exhibit a beneficial effect on the clinical manifestations, and which was the outcome?