The continuum of POLG-related diseases, which collectively represent the most prevalent group of nuclear-encoded PMDs, includes Alpers’ syndrome [1, 7, 28], which typically presents in infancy or adolescence with refractory epilepsy, and adult-onset POLG-related disease which may present with ataxia neuropathy spectrum (ANS), epilepsy, and chronic progressive external ophthalmoplegia (CPEO) [10, 11, 36]. This evidence concerns the gene POLG and External ophthalmoplegia.