PLA2G6-associated neurodegeneration: A phenotypic continuum

• DOI: 10.4103/aomd.aomd_53_24
• Publication Date: 2024-12-04T08:01:14Z
• Authors: Surabhi Garg; Nagashree Sharma; Chandrashekar H M; Kuldeep Shetty

Sir, PLA2G6-associated neurodegeneration (PLAN) is a subtype of Neurodegeneration with Brain Iron Accumulation (NBIA), caused by mutations in the PLA2G6 gene on chromosome 22q13.1. It traditionally manifests as three distinct phenotypes linked to age onset: infantile neuroaxonal dystrophy (INAD), atypical dystrophies (ANAD), and PLA2G6-related dystonia–parkinsonism (PLAN-DP).[1,2] We report an Indian case childhood onset features suggestive overlap PLAN. A 21-year-old boy presented history insidious-onset cervical dystonia at 7 years after short febrile illness. Five later, he developed right upper limb dystonic hand tremor. He had average scholastic performance until 20 years. then us 21 3-month subacute neurological worsening. The generalized, complained slowness activities sudden jerk-like involuntary movements. In addition, there was new cognitive behavioral changes form low mood, poor comprehension, difficulties finding words, navigational errors. patient second-degree consanguineous parentage, but no reported family similar On examination, testing revealed impairments attention, execution, working recent memory, visuospatial constructional tasks. Montreal Cognitive Assessment score 12/30. generalized involving trunk regions neck tremor, bradykinesia, myoclonic jerks limbs [Video 1]. There were pyramidal signs noted. Baseline part III motor Unified Parkinson's Disease Rating Scale (UPDRS) 41 out 108 Burke–Fahn–Marsden Dystonia (BFMD) 19. possibility recessive considered. Subacute psychiatric symptoms could either reflect worsening underlying condition or be unrelated etiologies, possibly infectious, immune, inflammatory. Investigations aimed rule latter causes. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_3uhdi8l4"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Routine tests normal. magnetic resonance imaging (MRI) showed mild cerebral atrophy, notably, iron accumulation [Figures 1 2]. Cerebrospinal fluid analysis whole-body positron emission tomography scan unremarkable. electroencephalogram (EEG) epileptiform discharges, although clear seizures. Whole-exome sequencing homozygous missense variation c.2264G>A (p.Arg755Gln) exon 16 gene. treated levodopa 300 mg per day clonazepam 0.5 day. Trihexyphenidyl avoided view concerns. At follow-up, UPDRS improved 11 from BFMD 9.5 dyskinesias 1-year follow-up.Figure 1: MRI FLAIR image normalFigure 2: Susceptibility Weighted Imaging did not show accumulationThe INAD phenotype PLAN has psychomotor regression early axial hypotonia, late spasticity, bulbar dysfunction, death 10 ANAD presents later between 1.5 6.5 language difficulty cerebellar, pyramidal, extrapyramidal dysfunction rapid deterioration end first decade. pathological hallmark axonal degeneration distended axons present throughout central peripheral nervous system. shows characteristic deposition globus pallidus and/or substantia nigra.[1,2] PLAN-DP variant usually second third Presentation may isolated onset, prior appearance symptoms, making diagnosis challenging. Parkinsonism develops decade; it good responsiveness result complications few weeks "tell-tale" levodopa-induced dyskinesias. other manifestations include dystonia, cortical myoclonus, ataxia, oculomotor involvement, signs. EEG abnormalities observed are infrequently noted adult-onset phenotype. Apart symptomatic treatment levodopa, deep brain stimulation targeting subthalamic nucleus internus shown promising results. However, reporting bias lack long-term outcome data limiting factors, underscoring need for further research provide stronger evidence.[2] After ruling possible contributors, this concluded following features: 1) An initial decade consistent presentation 2) Motor neuropsychiatric issues only 3) which more commonly than 4) Absence dyskinesia, frequent This mutation (c.2264G>A (p.Arg755Gln)) been INAD.[3] Moreover, same have different pedigree, suggesting that factors contribute disease course.[1-3] Table summarizes previously described cases overlapping highlighted last rows.[1,4-6]Table Review PLANThis review existing literature highlights can continuum spectrum rather age-related rigid phenosubtypes. More dystonia–parkinsonian disorders protracted course will help better understand such rare genetic disorders. Declaration consent authors certify they obtained all appropriate forms. patient(s) has/have given his/her/their images clinical information journal. patients their names initials published due efforts made conceal identity, anonymity cannot guaranteed. Acknowledgement acknowledge his cooperation. Author contribution Each author contributed patient's treatment, composition writing manuscript, provided critical revisions text. Research project: Conception: SG, KS Organization: CHM, NS, Execution: Statistical analysis: Design: Critique: Manuscript preparation: Writing draft: Ethical compliance statement work conducted ethical standards, institutional board approval required. secured informed subject publication material. reviewed journal's guidelines attest submission adheres them. Financial support sponsorship Nil. Conflicts interest conflicts interest.