PLA2G6-associated neurodegeneration in four different populations-case series and literature review

Parkinsonism Relat Disord. 2022 Aug:101:66-74. doi: 10.1016/j.parkreldis.2022.06.016. Epub 2022 Jun 30.


Background: PLA2G6-Associated Neurodegeneration, PLAN, is subdivided into: Infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and adult-onset dystonia parkinsonism [1]. It is elicited by a biallelic pathogenic variant in phospholipase A2 group VI (PLA2G6) gene. In this study we describe new cases and provide a comprehensive review of previously published cases.

Methods: Eleven patients, from four different institutions and four different countries. All underwent a comprehensive chart review.

Results: Ages at onset ranged from 1 to 36 years, with a median of 16 and a mean of 16.18 ± 11.91 years. Phenotypic characteristics were heterogenous and resembled that of patients with infantile neuroaxonal dystrophy (n = 2), atypical neuroaxonal dystrophy (n = 1), adult-onset dystonia parkinsonism (n = 1), complex hereditary spastic paraparesis (n = 3), and early onset Parkinson's disease (n = 2). Parental genetic studies were performed for all patients and confirmed with sanger sequencing in five. Visual evoked potential illustrated optic atrophy in P4. Mineralization was evident in brain magnetic resonance imaging of P1, P2, P4, P5, P7, and P11. Single photon emission computed tomography was conducted for three patients, revealed decreased perfusion in the occipital lobes for P10. DaTscan was performed for P11 and showed decreased uptake in the deep gray matter, bilateral caudate nuclei, and bilateral putamen. Positive response to Apomorphine was noted for P10 and to Baclofen in P2, and P3.

Conclusions: PLAN encompasses a wide clinical spectrum. Age and symptom at onset are crucial when classifying patients. Reporting new variants is critical to draw more attention to this condition and identify biomarkers to arrive at potential therapeutics.

Keywords: Adult-onset dystonia parkinsonism; Atypical neuroaxonal dystrophy; Infantile neuroaxonal dystrophy; Neurodegeneration with brain iron accumulation; Phospholipase A2 group VI.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Dystonic Disorders*
  • Evoked Potentials, Visual
  • Group VI Phospholipases A2 / deficiency
  • Group VI Phospholipases A2 / genetics
  • Humans
  • Infant
  • Iron Metabolism Disorders
  • Mutation
  • Neuroaxonal Dystrophies* / diagnostic imaging
  • Neuroaxonal Dystrophies* / genetics
  • Parkinsonian Disorders* / diagnostic imaging
  • Parkinsonian Disorders* / genetics
  • Phenotype
  • Young Adult


  • Group VI Phospholipases A2
  • PLA2G6 protein, human

Supplementary concepts

  • Dystonia-Parkinsonism, Adult-Onset
  • NBIA2B