Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration

Michael C. Kruer, Mark Hiken, Allison Gregory, Alessandro Malandrini, David Clark, Penny Hogarth, Marjorie Grafe, Susan J. Hayflick, Randall L. Woltjer

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Pantothenate kinase-associated neurodegeneration is a form of neurodegeneration with brain iron accumulation, characterized by a progressive movement disorder and prominent iron deposition in the globus pallidus. Formerly referred to as Hallervorden-Spatz syndrome, the disorder was renamed pantothenate kinase-associated neurodegeneration after discovery of the causative gene, PANK2. Although the pathological features of clinically characterized Hallervorden-Spatz syndrome have been described, the literature is confounded by the historical use of this term for nearly all conditions with prominent basal ganglia iron accumulation and by the fact that this term encompasses a genetically heterogeneous group of disorders, now referred to as 'neurodegeneration with brain iron accumulation'. As a result, interpreting reports that precede molecular characterization of specific forms of neurodegeneration with brain iron accumulation is problematic. In the present studies, we describe neuropathological findings in six cases of molecularly confirmed pantothenate kinase-associated neurodegeneration. We identify prominent ubiquinated deposits in pantothenate kinase-associated neurodegeneration. We also characterize two distinct origins of spheroid bodies and delineate histological features of iron deposition. In so doing, we characterize fundamental features of the disease and redefine its nosological relationship to other neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)947-958
Number of pages12
JournalBrain
Volume134
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Hallervorden-Spatz
  • neuropathology
  • pantothenate kinase-associated neurodegeneration (PKAN)
  • tau
  • α-synuclein

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint Dive into the research topics of 'Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration'. Together they form a unique fingerprint.

  • Cite this