POLG and Alpers syndrome: In agreement with this hypothesis, there are over 80 pathogenic mutations in the human POLG gene, and some of these are associated with Alper’s syndrome, PEO (progressive external ophthalmoplegia), or ataxia, and cause a variety of symptoms, including ophthalmoplegia, cataracts, hearing loss, progressive muscle weakness, parkinsonism, and cardiac dysfunction [22–23].