Objective: To report a case of a novel mutation in the PLA2G6 gene resulting in early-onset Parkinson’s Disease.

Background: The phospholipase A2 group VI (PLA2G6) gene encodes for an enzyme, phospholipase A2, that is involved in phospholipid remodeling, apoptosis, and prostaglandin and leukotriene synthesis. Mutations in this gene are implicated in a spectrum of autosomal recessive neurodegenerative diseases known as PLA2G6-associated neurodegeneration (PLAN), which includes infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and adult-onset PLAN. Adult-onset PLAN has multiple phenotypes, including PLA2G6-related dystonia-parkinsonism (PARK14), early-onset Parkinson’s Disease, hereditary spastic paraparesis, and ataxia.

Method: A 35-year-old Cuban male was in his usual state of health until the age of 30 when he started complaining of left upper extremity tremor. Over time he developed bradykinesia and rigidity of the left upper and bilateral lower extremities. Ancillary examinations included a normal brain MRI without radiologic evidence of iron accumulation and an abnormal DAT scan showing reduced dopaminergic uptake in the striatum bilaterally. The patient was diagnosed with early-onset Parkinson’s Disease. The patient achieved good symptomatic response to carbidopa/levodopa. He is also self-medicating with mucuna pruriens, which as per patient, offers a smoother onset and offset. At present, parkinsonism is at stage 2 on the Hoehn and Yahr scale. His course has been complicated by motor fluctuations, peak dose dyskinesias, impulse control disorder, depression, and anxiety.

Results: Genetic testing for 29 genes associated with Parkinson’s Disease revealed two heterozygous mutations in the PLA2G6 gene. The first variant was pathogenic, c.1903 C>T in exon 14, which has previously been described as a nonsense pathogenic variant suspected to cause protein truncation or nonsense mediated decay. The second variant was identified as c.-45-13 C>A in intron 1, which has not been previously described in the literature, nor seen in the general population. Parental studies to identify the phase of this variant are underway but due to the phenotype, which is consistent with PLA2G6, we interpret this variant as pathogenic leading to autosomal recessive PLA2G6 early-onset Parkinson’s Disease.

Conclusion: We have identified a novel mutation of the PLA2G6 gene in a patient presenting with early-onset Parkinson’s Disease.

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-pla2g6-mutation-presenting-as-early-onset-parkinsons-disease/