Case Report: A case of PLA2G6 gene-related early-onset Parkinson's disease and review of literature

Abstract

BackgroundEarly onset Parkinson's disease (EOPD) is a neurodegenerative disease associated with the action ofto genetic factors. A mutated phospholipase A2 type VI gene (PLA2G6) is considered to be one of pathogenic genes involved in EOPD development. Although EOPD caused by a mutated PLA2G6 has been recorded in major databases, not all mutant genotypes have been reported. Here, we report a case of PLA2G6-related EOPD caused by a novel compound heterozygous mutation.Case presentationThe case was an of 26-year-old young male with a 2-year course of disease. The onset of the disease was insidious and developed gradually. The patient presented with unsteady walking, bradykinesia, unresponsiveness, and decreased facial expression. Auxiliary examination showed a compound heterozygous mutation of the PLA2G6gene with c.991G > T and c.1427 + 1G > A. Mild atrophy of the cerebrum and cerebellum was detected on brain MRI. The patient was diagnosed with EOPD. We administered treatment with Madopar, which was effective. After a two-year disease course, we observed progression to stage 5 according to the Hoehn-Yahr Scale (without medicine in the off-stage). An MDS-UPDRS III score of 62 was obtained, with characteristics of severe disease and rapid progress. The diagnosis was an EOPD phenotype caused by a combination of mutations at the c.991G > T and c.1427 + 1G > A sites of the PLA2G6gene.ConclusionAfter active treatment, the disease was set under control, with no significant progression during the three-month follow-up period. Dyskinesia did not recur after reducing the Madopar dose. The freezing sign was slightly decreased and the wearing-off was delayed to 2 h.

A novel variant of PLA2G6 gene related early-onset parkinsonism: a case report and literature review

“…Furthermore, the initial symptoms were atypical and the clinical manifestations were milder. All of them were sensitive to levodopa treatment, which was consistent with previous studies ( 3 , 11 , 16 ). In addition, this study found that almost all of the probands with compound heterozygous mutations at this variant had cerebellar atrophy, while no cerebellar atrophy occurred in the six homozygous mutant probands, further suggesting that the clinical manifestations of patients with homozygous mutations at this variant were relatively mild.…”

“…Although the incidence of EOP is not high, the morbidity and mortality are very high ( 38 ), and most patients have a good response to treatment such as madopar 5–10 years after onset ( 3 ). This study also found that the vast majority of PLA2G6 gene-related EOP responds to levodopa treatment, but the delayed use of levodopa will increase the incidence of dyskinesia, and the switching period fluctuation is more obvious ( 33 ).…”

“…Because the sample size of most studies on PLA2G6 gene-related EOP in Chinese population is relatively small ( 3 , 16 , 27 ), this leads to limitations in the clinical and phenotypic comparison of different PLA2G6 gene mutation reviews in this study. The clinical and genetic characteristics of PLA2G6 gene-related EOP patients in China will be more clear in future multicenter large sample studies.…”

“…PLA2G6 gene mutation is considered to be one of the pathogenic genes involved in the development of EOP ( 1 ). Autosomal recessive EOP caused by mutations in the PLA2G6 gene is called PLA2G6-associated Neurodegeneration (PLAN) ( 2 , 3 ). These include Infantile neuroaxonal dystrophy (INAD), Atypical neuroaxonal dystrophy (ANAD), and EOP ( 4 ).…”