Objective: To report a Parkinson’s disease (PD) patient with PRKN mutation initially diagnosed with dopa-responsive dystonia (DRD), unmasked after developing signs of parkinsonian disease progression.

Background: Most PD cases are sporadic, and monogenic forms account for approximately <5% of sporadic cases. PRKN (also known as PARK2) mutation is the most common cause of autosomal recessive early-onset PD, with first symptom usually manifesting before age of 40 years. PD patients with parkin mutation may experience isolated lower-limb dystonia for years. This can mimic motor phenotype of DRD. Globus pallidus interna (GPi) deep brain stimulation (DBS) may benefit selected patients with PARK2 mutation who experience motor fluctuations with oral levodopa therapy.

Method: Case study

Results: We describe a 43 year-old man initially diagnosed with DRD at age of 8 years following onset of right foot dystonia that responded to levodopa challenge. No genetic tests were commercially available at the time of diagnosis. Patient remained well-controlled on a low dose of levodopa until the age of 40, when he developed severe motor fluctuations and dyskinesias. He underwent bilateral GPi DBS placement at outside facility. Upon referral to our tertiary movement disorder center, presence of dystonia and parkinsonism with motor fluctuations raised concerns for young-onset PD. Genetic testing confirmed homozygous pathogenic variant of PARK2.

Conclusion: Challenges of differentiating very early-onset PD (or juvenile PD, with age of onset <20 years) from DRD are well recognized. Both conditions can present as dystonia, with early levodopa response. Our patient had a positive levodopa response for decades before onset of motor fluctuations and dyskinesias, which are often associated with advanced PD. Early differential diagnosis is critical given distinct long-term treatment and prognosis of these disorders. This report also highlights the importance of genetic testing in distinguishing parkin type early-onset PD from DRD. More research is needed to evaluate how genotype influences DBS outcomes in patients with hereditary forms of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prkn-positive-parkinsons-disease-masked-as-dopa-responsive-dystonia/