Objective: To describe a patient with atypical parkinsonism, carrier of a rare PLA2G6 gene variant.

Background: PLA2G6-associated neurodegeneration (PLAN) results from mutations in PLA2G6 gene and comprises three different phenotypes: infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, as well as PLA2G6-related dystonia-parkinsonism. The latter is characterized by an early age of onset (before age 40) parkinsonism with dystonia, cognitive decline and psychiatric symptoms. Recently, hererozygous PLA2G6 mutations have been related to iron accumulation within basal ganglia and Parkinson’s disease.

Method: A 51-year-old male presented with bilateral rest and action tremor, bilateral asymmetric bradykinesia and rigidity. In the clinical interview, a REM sleep behavior disorder was detected. Previous medical history included a bipolar disorder treated with lithium.  Under the clinical suspicion of Parkinson’s disease, dopaminergic treatment was initiated, with a partial response. Brain MRI showed brain atrophy and claval hypertrophy. Iron deposits were not observed. A dopamine-transporter SPECT showed a reduced bilateral tracer uptake in the striatum.  The parkinsonism progressed in the following months with more severe bradykinesia and tremor. The dopaminergic treatment was increased up to 16 mg of rotigotine and 600 mg of levodopa within the first three years of disease, with a slight improvement in the symptoms. A dysexecutive mild cognitive impairment, depression and erectile dysfunction appeared.

Results: A rare, heterozygous missense variant in the PLA2G6 gene (c.773C>T p.Ser258Leu; c.239C>T p.Ser80Leu) of uncertain significance was detected by targeted next-generation sequencing.

Conclusion: Our findings support that heterozygous variants in the PLA2G6 gene could be associated with atypical adult-onset parkinsonism. Genetic testing of patients with atypical parkinsonian syndromes, especially when some radiological signs are present could help to a better characterization of the PLAN clinical spectrum.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/atypical-parkinsonism-related-to-a-rare-variant-in-the-pla2g6-gene/