Objective: To report a novel case of early-onset parkinsonism due to a presenilin 1 gene (PSEN1) mutation.

Background: Mutations in PSEN1 gene are the most common genetic cause of early-onset Alzheimer´s disease (AD). We present a patient with an atypical clinical presentation.

Method: A 38 y/o male complained of kinetic tremor and slowness of left hand. Apathy and mood disorder started before motor symptoms and previously he suffered REM behavior disorder. On examination he presented left rigidity and bradykinesia, postural tremor as well as a dystonic posture with myoclonus of the left hand.
In a 2-year follow-up period, the parkinsonism progressed affecting also the right hemibody, left Pisa posture and postural instability with frequent falls. He developed cognitive impairment affecting language production, memory and executive functions as well as visual hallucinations and disorientation.
He experienced initial moderate improvement with levodopa treatment, presenting motor fluctuations since the beginning. Duloxetine and rivastigmine were added with partial mood and cognitive improvement.
On last examination, he presented dysarthria and hypofluent language, oculomotor and ideomotor apraxia, severe asymmetric parkinsonism, parkinsonian gait with freezing of gait and intense multifocal spontaneous myoclonus.
Regarding the family history, his mother suffered an early-onset dementia. His grandmother and two of her sisters presented dementia as well.

Results: CSF findings were consistent with AD (increased of P-Tau and decreased β-amyloid and ratio β_1-42/β_1-40). DAT-SPECT showed significant hypodensity of dopamine transporter in the bilateral putamen (predominantly right) and right caudate nucleus. Brain MRI showed atrophy in the bilateral parieto-occipital cortex with spare of medial temporal lobe. ¹⁸F-FDG-PET showed bilateral parieto-temporo-occipital hypometabolism (including precuneus and posterior cingulate cortex) and striatum hypermetabolism. ¹⁸F-florbetaben-PET showed cortical amyloid deposition in precuneus/posterior cingulate, lateral temporal, frontal and parietal lobes.
In genetic testing a heterozygous pathogenic variant was identified in the PSEN1 gen (c,488A>G, p.H163R).

Conclusion: Parkinsonism in a young adult may be an uncommon presentation of a PSEN1 mutation. Therefore, PSEN1 gene should be considered in the genetic panel for early-onset Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/asymmetric-early-onset-parkinsonism-due-to-psen1-mutation/