Autosomal recessive TWNK mutations have been linked to infantile-onset spinocerebellar ataxia (IOSCA) and hepatocerebral depletion disorder, whereas dominant TWNK mutations are characterized by progressive external ophthalmoplegia (PEO) and ptosis in most patients, typically with an adult-onset presentation. Here, TWNK is linked to mitochondrial DNA depletion syndrome 7 (hepatocerebral type).