POLG1-related levodopa-responsive parkinsonism

• We assesses the longitudinal clinical features and levodopa response of three patients with neurodegenerative parkinsonism who harbor POLG1 mutations.
• Our observations expand the genotypic and phenotypic spectrum of POLG1-related parkinsonism to include two novel POLG1 mutations.
• The role of mitochondrial DNA defects in the pathogenesis of neurodegenerative parkinsonism.

Parkinsonian features have been described in patients with POLG1 mutations. Notwithstanding, the clinical expression has been revealed heterogeneous and the response to dopaminergic treatment has been document in few cases. We aim to describe the longitudinal clinical features and the treatment response of three unrelated patients with neurodegenerative parkinsonism, preceded by PEO and SANDO syndromes, who harbor POLG1 mutations, including two novel mutations. It was documented a sustained response to levodopa, at 3 and 8 years of follow-up of parkinsonian syndrome, and reduced striatal dopamine uptake. We review the genotypic and phenotypic spectrum of POLG1-related parkinsonism. Our observations stimulate the debate around the role of mitochondrial DNA defects in the pathogenesis of neurodegenerative parkinsonism.