POLG1 mutations are responsible for multiple clinical diagnoses with overlapping phenotypes. Aside from Autosomal Dominant Progressive External Ophthalmoplegia, all of the other conditions are inherited in an autosomal recessive manner.
Alpers-Huttenlocher syndrome (AHS) includes a progressive and severe encephalopathy with epilepsy, neuropathy and liver failure.
Childhood Myocerebrohepatopathy Spectrum (MCHS) presents before age three with developmental delay, lactic acidosis, failure to thrive and myopathy. Hearing loss, cyclic vomiting, renal and hepatic problems are also often present.
Myoclonic Epilepsy Myopathy Sensory Ataxia (MEMSA) includes myopathy, epilepsy and ataxia without ophthalmoplegia and generally presents in young adulthood.
Ataxia Neuropathy Spectrum (ANS) includes mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). Features include ataxia, neuropathy and often encephalopathy with seizures.
Autosomal Recessive Progressive External Ophthalmoplegia (arPEO) involves progressive PEO without systemic involvement.
Autosomal Dominant Progressive External Ophthalmoplegia (adPEO) involves progressive weakness of the extraocular eye muscles which causes strabismus and ptosis.