Levodopa response in Parkinsonism with multiple mitochondrial DNA deletions

Area of Science:

• Neurology
• Genetics
• Mitochondrial Biology

Background:

• Autosomal dominant chronic progressive external ophthalmoplegia is a rare neuromuscular disorder.
• Mitochondrial DNA (mtDNA) deletions can cause various neuromuscular phenotypes.
• Genetic causes for familial external ophthalmoplegia include mutations in POLG, ANT-1, and Twinkle.

Observation:

• A patient presented with chronic progressive external ophthalmoplegia and prominent Parkinsonism.
• The patient exhibited prolonged benefit from levodopa (L-dopa), followed by L-dopa-induced dyskinesias and motor fluctuations.
• Family linkage analysis excluded mutations in POLG, ANT-1, and C10orf2 (Twinkle) as the cause.

Findings:

• The patient had multiple mtDNA deletions in muscle tissue.
• The clinical presentation mimicked idiopathic Parkinson's disease, including L-dopa responsiveness.
• This case demonstrates that L-dopa responsiveness and fluctuations can occur in mitochondrial disease-associated Parkinsonism.

Implications:

• Mitochondrial disease should be considered in the differential diagnosis of atypical Parkinsonism, especially with ophthalmoplegia.
• Levodopa treatment response and complications may be observed in mitochondrial Parkinsonism, similar to other atypical parkinsonian syndromes.
• Further research is needed to understand the genetic and molecular mechanisms linking mtDNA deletions to Parkinsonism.