Mutations in the gene coding for the catalytic subunit of mtDNA polymerase (POLG) are associated with a range of syndromes characterized by secondary mtDNA defects, including mtDNA depletion and multiple deletions (Mitochondrial DNA depletion syndrome 4B, MNGIE type; OMIM # 613662) [29]. This evidence concerns the gene POLG and mitochondrial neurogastrointestinal encephalomyopathy.