Objective: PLA2G6-associated neurodegeneration (PLAN) is a rare form of neurodegeneration with brain iron accumulation (NBIA) leading to heterogeneous clinical manifestation including infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and early-onset dystonia-parkinsonism (EODP).  EODP encompasses broad spectrum of symptoms including parkinsonism, dystonia, cerebellar ataxia, psychiatric disturbances or cognitive decline. We here described a rare case of PLA2G6 related EOPD and discussed the clinical and radiological clues for differential diagnosis.

Background: A 29-year-old young woman presented to our hospital with balance problems leading to falls that started seven years ago, and severe stiffness and slowliness of movements accompanied within the last 4 years. She had a severe disabling postural instability enabling her to walk without assistance for the last two years. Her family history was unremarkable.

Method: On neurological examination she had severe bilateral bradykinesia and rigidity with severe postural instability leading to falls. Mild-to-moderate dystonic posturing of the feet and the legs was remarkable. She had mild mental bluntness.

Results: She had mild levodopa response with dyskinesia at low doses. Laboratory investigations including Wilson’ s disease screening were normal.  Brain magnetic resonance imaging (MRI) of the patient revealed hyperintensities in the globus pallidus at the T2-weighed axial images and cerebellar atrophy and claval hypertrophy in the midline sagittal T1-weighed images supportive of neurodegeneration with brain iron accumulation (NBAI). Whole exome sequencing (WES) of the patient revealed a homozygous missense mutation in the PLA2G6.

Conclusion: PLAN is a rare disease caused by mutations in the ubiquitously expressed PLA2G6 gene characterised by the presence of axonal spheroids and progressive brain iron deposition and clinically by progressive motor dysfunction and cognitive decline. Owing to the highly variable clinical manifestations and the lack of specific clinical criteria for diagnosis, it is important to raise awareness on PLAN, a rare subtype of NBIA, and a suspicion for PLAN should arise based on the age of presentation, clinical features, and radiological findings prompting consideration for genetic testing to confirm the subtype to establish proper treatment approach.

References: 1. Karkheiran S, Shahidi GA, Walker RH, Paisán-Ruiz C. PLA2G6-associated Dystonia–Parkinsonism: Case Report and Literature Review. Tremor Other Hyperkinet Mov (N Y) 2015 Jul 10;5:317. doi: 10.7916/D84Q7T4W.
2. Cheng Y, Zhang Y, Xiao Y, Wang S, Chen S, Zheng X, Yang T, Jiang Q, Huang J, Y, Ou R, Li C, Wei Q, Chen X, Shang H. Clinical and genetic characteristics of PLA2G6-related parkinsonism in Southwest China and a comprehensive literature review. J Med Genet 2025 Jul 21;62(8):508-515. doi: 10.1136/jmg-2024-110479.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-rare-case-of-pla2g6-gene-related-early-onset-dystonia-parkinsonism-what-not-to-miss-clinically-and-radiologically/