Mutations in nuclear genes which encode proteins involved in mitochondrial DNA (mtDNA) replication or maintenance can cause mtDNA depletion or multiple mtDNA deletions in post-mitotic tissue, causing a range of mitochondrial diseases. Mutations in two such genes, POLG, which encodes the catalytic subunit of the mitochondrial polymerase gamma and C10orf2, which encodes Twinkle, a DNA helicase, are typically associated in adults with autosomal dominant or recessive CPEO, and very rarely, CPEO and Parkinsonism [1, 2]. Here, we describe our findings in two patients with late-onset CPEO, white matter changes and Parkinsonism. Patient-1 presented at age 63 years with CPEO, ptosis, congenital cataracts, vision loss with macular degeneration, hearing loss, dysarthria, dysphagia, sensorimotor polyneuropathy, fatigue, migraine, cardiomyopathy and depression. At age 67, he developed asymmetric resting tremor and impaired balance. Examination at age 71 revealed CPEO, facial diplegia, mild symmetric rigidity, intermittent, predominantly right-sided resting tremor and multidirectional head tremor, bradykinesia, and ataxic gait (broad based stance with inability to tandem). Total baseline UPDRS Part III was 26. Treatment with carbidopa/levodopa (25/ 100 mg three times daily) improved the symptoms (reduction of total UPDRS III to 14) but was not sufficiently tolerated, and the tremor was subsequently stabilized with low dose clonazepam. Motor symptoms have remained stable over the last three years. Brain MRI showed mild atrophy and very subtle multifocal subcortical white matter lesions (Fig. 1a–c). Family history was positive for congenital cataracts, thyroid disease, and premature menopause (age 27) in his daughter, who declined genetic testing. Muscle biopsy (quadriceps) showed chronic myopathic changes, subsarcolemmal accumulation of mitochondria, some containing paracrystalline inclusions, and multiple mtDNA deletions following southern blotting. Sequencing of POLG revealed a heterozygous c.2828G [A; p.Arg943His mutation in exon 18, previously described in two families with autosomal dominant CPEO, in one together with primary ovarian failure [1, 3]. Patient-2, a 74 year old man with a 10 year history of bilateral ptosis, slowly progressive bilateral CPEO, progressive left-sided ‘‘weakness,’’ mild, proximal myopathy and fatigue on exertion, presented at age 66 with reduced dexterity and nocturnal muscle cramps. Four years later, he developed mild, asymmetric, predominantly left-sided Parkinsonism including hypomimia, mild resting tremor, and moderate bradykinesia, with UPDRS scores as follows: Part I (2), Part II (8), Part III (10). Cerebral DAT scan revealed reduced striatal dopamine uptake. He declined dopaminergic treatment. The motor symptoms have remained stable over the last four years. Brain MRI demonstrated mild, non-specific white matter lesions (Fig. 1d–f). Family history was negative for CPEO and Parkinsonism. Muscle biopsy (quadriceps) revealed a predominance of type II fibres, some fibres with numerous central nuclei, some cytochrome oxidase negative fibres, and multiple B. R. Brandon M. Soni Rush University Medical Center, Chicago, IL, USA