Neurodegeneration with Brain Iron Accumulation

Iron participates in a wide array of cellular functions and is essential for normal neural development and physiology. However, if inappropriately managed, the transition metal is capable of generating neurotoxic reactive oxygen species. A number of hereditary conditions perturb body iron homeostasis and some, collectively referred to as neurodegeneration with brain iron accumulation (NBIA), promote pathological deposition of the metal predominantly or exclusively within the central nervous system (CNS). In this chapter, we discuss ten NBIA disorders with emphasis on the clinical syndromes and neuroimaging. The latter primarily entails magnetic resonance scanning using iron-sensitive sequences. The conditions considered are pantothenate kinase 2-associated neurodegeneration (PKAN), neuroferritinopathy, aceruloplasminemia, Kufor-Rakeb disease (KRD), PLA2G6-associated neurodegeneration (PLAN), FA2H-associated neurodegeneration (FAHN), Woodhouse-Sakati syndrome (WSS), beta-propeller protein-associated neurodegeneration (BPAN), mitochondrial membrane protein-associated neurodegeneration (MPAN), and coenzyme A synthase protein-associated neurodegeneration (CoPAN). An approach to differential diagnosis and the status of iron chelation therapy for several of these entities are presented.