Summary

Mutations in POLG1 are an important cause of human mitochondrial disease. We describe a woman who presented with bilateral ptosis and external ophthalmoplegia at 64 years of age. Neurological examination revealed symptoms of diffuse encephalopathy. The symptoms were progressive and at 67 years she was severely cognitively impaired, had severe bilateral ptosis and complete external ophthalmoplegia. Frequent cytochrome c oxidase-negative fibres were detected in muscle. Electrophysiological examination revealed myopathic changes and axonal neuropathy. Standard laboratory tests were normal. Brain CT showed general, moderate cortical atrophy. Molecular analysis of muscle DNA revealed multiple mitochondrial DNA deletions. Sequencing of the entire POLG1 gene revealed two changes c.2993C>T (p.998S>L) and c.3550G>C (p.1184D>H). Both mutations are previously unreported and confirmed to be compound heterozygous. Late-onset progressive external ophthalmoplegia with severe encephalopathy is an unusual combination in patients with POLG1 mutations. POLG-associated disease should be considered in any patient with unexplained or unusual neurological features.