POLG-related disorders consist of multiple inherited disorders with broad and overlapping symptoms affecting many tissues and organs, especially brain, nerves, muscle, and liver. These disorders are caused by the deficiency of DNA polymerase gamma, the enzyme required for mitochondrial DNA synthesis. Ages of onset range from early childhood to adulthood and many individuals have some, but not all, of the symptoms of one or more of the individual disorders. Alpers syndrome, the most severe and prevalent form in the spectrum of POLG-related disorders, is characterized by seizures, loss of mental and movement abilities, and liver disease. People with Alpers syndrome usually begin symptoms before age four years and survive for 3 months to 12 years after onset of the first symptoms. Autosomal dominant progressive external ophthalmoplegia (PEO) is an adult-onset POLG-related disorder, which causes the eyelids to droop. Symptoms and severity are not predictable based on the pathogenic variants present in a person. There is no cure for POLG-related disorders but medical surveillance and care may help to improve some symptoms and overall condition of life. Some medicines for epilepsy treatment may make liver disease much worse and should be avoided. POLG-related disorders are caused by pathogenic variants in the POLG gene.