Objective: To describe the evidence for severe dopaminergic deficit in early stages of genetically confirmed Perry syndrome

Background: PS is a neurodegenerative disease comprised of a constellation of parkinsonism, neuropsychiatric symptoms, weight loss, and central hypoventilation. PS is inherited in an autosomal dominant manner and caused by mutations in the DCTN1 gene, which encodes the largest subunit of dynactin.  It is characterized pathologically by the inclusion of TAR DNA-binding protein43 (TDP-43) in neurons and glial cells.

Parkinsonism with rigidity, bradykinesia, and postural imbalance are commonly presenting symptoms, and levodopa responsiveness is variable. Dopaminergic imaging in these patients is rarely reported, but signs of presynaptic dopaminergic deficit is expected in these patients.

Method: Case report with a literature review.

Results: A 43-year-old male presented with three-year history of poor concentration, slowness of movements and unsteadiness. Two years since the onset he started to experience falls, mostly backwards. Clinical examination at age 41 showed relatively symmetrical mild hypokinetic rigid syndrome with a mild bilateral rest tremor. He was started on levodopa and the daily dose of 600 mg has improved his parkinsonism with less rigidity and bradykinesia.

He reported a history of PS in his father, but no other details were available. Genetic testing detected Thr72Pro mutation in the DCTN1 gene that was previously reported in PS.

DAT scan was obtained one year after the onset of his motor symptoms. He had two scans 60 days apart to exclude a possibility of artifacts. Both studies demonstrated no detectable uptake in the basal ganglia, indicating severe dopaminergic presynaptic deficit. He was not on any medications known to interfere with DAT scan. He stopped bupropion 10 days before the first scan, and it was never restarted.

Conclusion: Our report demonstrates very severe presynaptic dopaminergic denervation even in early clinical stages of PS. This provides further insights into the pathogenesis of Parkinsonism in PS, suggesting marked neurodegeneration before the onset of clinical symptoms of PS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/severe-dopaminergic-deficits-in-early-stage-genetically-confirmed-perry-syndrome/