Abstracts from the Fourth International Symposium on Neuroacanthocytosis
July 1-2, 2008
London and Oxford
Chairs: Prof. Kailash Bhatia, MD, FRCP, Institute of Neurology, University College London; Prof. Anthony P. Monaco, MD, PhD, Wellcome Trust Centre for Human Genetics, University of Oxford
Organizers: Antonio Velayos-Baeza, PhD; Susanne Schneider, MD; Glenn Irvine
3-1 Pantothenate kinase-associated neurodegeneration (PKAN): Hypotheses of pathogenesis and relevance to other neuroacanthocytoses
S. J. Hayflick
Oregon Health & Science University, Portland, Oregon, USA
Pantothenate kinase-associated neurodegeneration (PKAN) is characterized by dystonia, pigmentary retinopathy, basal ganglia iron accumulation and acanthocyte formation. The causative gene, PANK2, is one of four human genes to encode a pantothenate kinase, the key regulatory protein in coenzyme A biosynthesis. Pantothenate kinase 2 is unique among these homologs for being targeted to mitochondria.
Disease caused by mutations in PANK2 is hypothesized to arise from a combination of stressors in the specialized cells and tissues affected in PKAN. These include energy demands, cellular and organellar membrane composition, differential activities of other pantothenate kinases, and compensatory mechanisms in the affected cells. Data will be presented to support a hypothesis of disease that centers on lipid dyshomeostasis. This mechanism is likely to underlie other disorders that share key features with PKAN.