Objective: We present a novel homozygous PLA2G6 mutation and response to Deep Brain Stimulation (DBS).

Background: Neurodegeneration with brain iron accumulation (NBIA) type 2/PLA2G6 is a rare disorder, known to cause an atypical early-onset parkinsonism and dystonia syndrome in patients with increased pallidal iron, but phenotypic variability is well known.

Methods: A 26 year-old male with mild learning difficulties and consanguineous parents was referred for left sided rest tremor and difficulty initiating gait for 3 years. He had levodopa responsive asymmetric rest tremor, rigidity and bradykinesia and pyramidal signs, mild freezing of gait and postural instability. Psychosis developed while on anticholinergics and dopaminergic agonists. Brain MRI was unremarkable and DaTscan® showed reduced right striatal uptake. Genetic testing for PARK2, PARK6, PARK8, PARK1 and Huntington’s disease was negative and for PARK7 and PARK14/NBIA2 showed: PLA2G6 homozygosity for c.1627C>T (p.Arg543Cys), not previously described and probably pathogenic, and heterozygosity for c.1077G>A (p.Met358Ilefs*); and DJ1 heterozygosity for c.88G>T (p.Gly30Trp), also not previously described. There was partial remission of psychosis after stopping anticholinergics and agonists, gradual worsening of parkinsonism and early development of severe choreic and dystonic dyskinesias and motor fluctuations. Brain MRI 5 years after disease onset showed bilateral pallidal hypointensity on T2*-weighted images.

Results: Preoperative levodopa response was 27% with severe freezing of gait, axial dystonia and postural instability in “off state” and autonomous gait in “on state”. He underwent GPi-DBS and at one-year follow-up there was an improvement in gait from not being able to walk alone to autonomous gait in “off” and “on” stimulation conditions, respectively.

Conclusions: We report a novel PLA2G6 mutation, c.1627C>T, associated with an early-onset levodopa responsive parkinsonism, dystonia, pyramidal and neuropsychiatric syndrome in which GPi-DBS helped in gait disturbance.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-pla2g6-c-1627ct-homozygous-mutation-and-response-to-dbs-gpi/