Cystic leukoencephalopathy and early-onset hypomyelinating leukodystrophies have also been reported in association with biallelic PNPT1 variants [25,36], as well as severe multisystemic presentations of Leigh syndrome and complex neurodegenerative phenotypes, including myoclonus, choreoathetosis, cerebellar ataxia, and optic atrophy [37,38]. Here, PNPT1 is linked to Leber hereditary optic neuropathy.