title: Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration.
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.
authors: Division of Developmental Paediatrics, Child Development and Rehabilitation Centre, Oregon Health and Science University, Portland, OR 97239, USA.
authors: Michael C
authors: MC
authors: Kruer
authors: Mark
authors: M
authors: Hiken
authors: Allison
authors: A
authors: Gregory
authors: Alessandro
authors: A
authors: Malandrini
authors: David
authors: D
authors: Clark
authors: Penny
authors: P
authors: Hogarth
authors: Marjorie
authors: M
authors: Grafe
authors: Susan J
authors: SJ
authors: Hayflick
authors: Randall L
authors: RL
authors: Woltjer
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D007501:Iron