Pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN): review of two major neurodegeneration with brain iron accumulation (NBIA) phenotypes

Int Rev Neurobiol. 2013;110:49-71. doi: 10.1016/B978-0-12-410502-7.00003-X.

Abstract

Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous group of disorders characterized by the presence of radiologically discernible high brain iron, particularly within the basal ganglia. A number of childhood NBIA syndromes are described, of which two of the major subtypes are pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN). PKAN and PLAN are autosomal recessive NBIA disorders due to mutations in PANK2 and PLA2G6, respectively. Presentation is usually in childhood, with features of neurological regression and motor dysfunction. In both PKAN and PLAN, a number of classical and atypical phenotypes are reported. In this chapter, we describe the clinical, radiological, and genetic features of these two disorders and also discuss the pathophysiological mechanisms postulated to play a role in disease pathogenesis.

Keywords: Neurodegeneration with brain iron accumulation (NBIA); PANK2; PLA2G6.

Publication types

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

MeSH terms

  • Animals
  • Brain / pathology*
  • Brain / physiopathology
  • Group VI Phospholipases A2 / genetics
  • Humans
  • Iron Metabolism Disorders* / genetics
  • Iron Metabolism Disorders* / pathology
  • Iron Metabolism Disorders* / physiopathology
  • Mutation
  • Neuroaxonal Dystrophies* / genetics
  • Neuroaxonal Dystrophies* / pathology
  • Neuroaxonal Dystrophies* / physiopathology
  • Pantothenate Kinase-Associated Neurodegeneration* / genetics
  • Pantothenate Kinase-Associated Neurodegeneration* / pathology
  • Pantothenate Kinase-Associated Neurodegeneration* / physiopathology
  • Phenotype
  • Phosphotransferases (Alcohol Group Acceptor) / genetics

Substances

  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase
  • Group VI Phospholipases A2
  • PLA2G6 protein, human

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)