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

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.

© 2013 Elsevier Inc. All rights reserved.

Figures

Figure 2.1

Radiological features of PKAN on brain MRI. Axial T2 (A) and axial FLAIR (B) images indicating the “eye-of-the-tiger” sign with medial globus pallidus hyperintensity (yellow arrow) surrounded by a region of hypointensity (blue arrow).

Figure 2.2

PLA2G6 and PANK2 enzymes: biochemical pathway and implicated cellular processes in PLAN and PKAN.

Figure 2.3

Radiological features of PLAN on brain MRI. Sagittal T1-weighted sequence (A) showing abnormal orientation of the posterior splenium of the corpus callosum (blue arrow), apparent claval hypertrophy (yellow arrow), and marked atrophy of the cerebellum (white arrow). T2-weighted sequences showing hypointensity in the globus pallidus (B) and substantia nigra (C), both indicated by yellow arrows. Note symmetrical white matter changes are evident on images (B) and (C), which can be reported in PLAN.