Reply to: Juvenile PLA2G6‐parkinsonism due to Indian ‘Asian’ p.R741Q mutation, and response to STN DBS

Abstract

We are grateful for Ravat et al.'s interest in our article on PLA2G6-parkinsonism. 1,2,3 They reported an additional case showing some clinicoradiological diagnostic hints we highlighted, including young onset of levodopa-responsive parkinsonism, occurrence of truncal dystonia and cerebellar signs, early development of levodopa-induced dyskinesia, and presence of cerebellar atrophy as well as possible lack of iron deposition on brain MRI. 2 Their case 1 reinforces our observation that NM_003560.4(PLA2G6):c.2222G > A (p. Arg741Gln) is the most frequent variant in Indian cases of PLA2G6-parkinsonism. 2 It also adds to the hitherto scant evidence that deep brain stimulation (DBS) may be effective for managing symptoms and early complications of dopaminergic treatment in this disorder. 1,2 Further cases of PLA2G6-parkinsonism are in keeping with the main findings of our work and confirm the core phenotype depicted therein, 2-7 including another patient we identified (Table 1, Case S1). This is a 35-year-old female born to consanguineous Pakistani parents after uncomplicated pregnancy and birth. She experienced occasional falls during childhood and required crutches because of lower-limb spasticity since her teenage years. Despite a mild learning difficulty, she completed her secondary education at a normal school. At age 16, she had a psychotic FIG. 1. Sagittal T1 (A) and axial T2 (B) magnetic resonance (MR) images show mild cerebellar atrophy. 99mTc-TRODAT SPECT scan (C) reveals bilateral, asymmetric reduction of tracer uptake, more prominent on the left side, with putaminal uptake more reduced than the caudate bilaterally, consistent with the pattern seen in Parkinson's disease. [Color figure can be viewed at wileyonlinelibrary.com]

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

“…The reported here results suggests that these characteristics are associated with the presence of a compound heterozygous mutation of the PLA2G6 gene with c.991G > T and c.1427 + 1G > A. Several studies have indicated that the rapid progression of the disease in EOPD patients may be related to the fluctuation of the hormone levels in the body (Magrinelli et al, 2022). However, this case had no obvious history of hormone fluctuations.…”

Levodopa‐Induced Jaw and Facial Dystonia in a Case of Progressive Supranuclear Palsy with Blepharospasm

“…Only a few authors reported levodopa‐induced OMD in a PD subject 7,8 . Besides, OMD has been reported in two cases with PLA2G6‐parkinsonism which is a recently defined, rare form of hereditary parkinsonism 9 . To our knowledge, there are only two published reports describing a PSP subject developing levodopa‐induced OMD 10,11 .…”

“…7,8 Besides, OMD has been reported in two cases with PLA2G6-parkinsonism which is a recently defined, rare form of hereditary parkinsonism. 9 To our knowledge, there are only two published reports describing a PSP subject developing levodopainduced OMD. 10,11 Tan et al reported a patient with PSP who developed levodopa-induced OMD after increasing levodopa dosage (to 300 mg/day) which completely resolved after discontinuation of levodopa.…”

A Comprehensive Examination of Human Brain Disorders

“…Despite several clinical studies, e.g. [6], that have shown evidence of the effectiveness of DBS in movement disorders treatment, there are still some unresolved issues that persist. The efficacy of DBS has been shown in people with PD who do not respond to medicinal treatment, leading to improvements in both the quality of life and motor function, as previously discussed.…”