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Iron Accumulation in Syndromes of Neurodegeneration with Brain Iron Accumulation 1 and 2 – causative or consequential?
  1. Susanne A Schneider (s.schneider{at}
  1. Neurogenetics Unit, University Hospital Luebeck, Germany
    1. John Hardy (j.hardy{at}
    1. Institute of Neurology, Queen Square, London, United Kingdom
      1. Kailash Bhatia (kbhatia{at}
      1. Institute of Neurology, Queen Square, London, United Kingdom


        Syndromes of Neurodegeneration with Brain Iron Accumulation (NBIAs) are inherited movement disorders characterized by a progressive degeneration of the nervous system. There has been recent progress in the work-up of these disorders. While for some of the NBIA disorders, such as neuroferritonopathy,1 causative mutations in genes involved in brain iron metabolism have been found, for the two core syndromes the link to iron remains could be speculated on. The two main NBIA syndromes are pantothenate kinase-associated neurodegeneration (PKAN, previously also called Hallervorden-Spatz disease or NBIA type 1) caused by mutations in the PANK2 gene on chromosome 202, and NBIA type 2, the condition of infantile neuroaxonal dystrophy due to mutations in the PLA2G6 gene located on chromosome 223;4In the following we will concentrate on the two autosomal recessive subtypes which are not directly related to the iron metabolism.The currently thought-to-be “classic” phenotype of thesedisorders, NBIA types 1 and 2, is that of a young-onset progressive extrapyramidal-pyramidal syndrome with visual disturbance.5 It has been claimed that iron deposition in the basal ganglia is one of the hallmark features; and hence, the term NBIA was coined. For PKAN, the deposition imaging pattern resembling an “eye of the tiger” has been proposed to be a characteristic, indeed pathognomonic, feature.5;6 Some have claimed that based on the MRI pattern alone, those with and those without PKAN mutations can be distinguished.5;6 Although there has been some debate about the nature of this MRI sign7;8, this is becoming accepted widely. Similar studies have been published for the second type of NBIA, elaborating on the exact pattern and time course of the iron deposition. All this appears to imply that iron plays a leading, indeed causative, role in the pathophysiological process in these disorders. However, the nature of iron accumulation in these NBIA syndromes is far from clear.

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