POLG and mitochondrial neurogastrointestinal encephalomyopathy: Since the first identification of mutations in POLG [16] and TWNK [18] as causative of MDDS in 2001, a total of 10 genes encoding proteins directly involved in mtDNA replication and repair machinery have been incorporated in this list to date, including the recent identification of mutations in LIG3 causing a mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) like phenotype [25].