Neurodegeneration with brain iron accumulation

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Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurological disorders in which iron accumulates in the basal ganglia, resulting in progressive dystonia, Parkinsonism, spasticity, optic atrophy or retinal degeneration and neuropsychiatric abnormalities. NBIA disorders have been associated with genes in synapse and lipid metabolism related pathways.[1] Describes a group of disorders characterized by an accumulation of brain iron and the presence of axonal spheroids in the central nervous system.[2] Iron accumulation can occur any where in the brain, with accumulation typically occurring in globus pallidus, substantia nigra, pars reticula, striatum and cerebellar dentate nuclei.[3] Symptoms can include various movement disorders, seizures, visual disturbances, and cognitive decline, usually in combination.[3] The known causes of NBIA disorders are mutations in genes directly involved in iron metabolism, impaired phospholipid and ceramide metabolism, lysosomal disorders, as well as mutations in genes with unknown functions.[3] Onset can occur at different ages, from early childhood to late adulthood.[3] Magnetic resonance imaging (MRI) is used to distinguish between the different forms of NBIA due to the accumulation of iron in different areas of the brain.[4] Patients typically fall into two different categories: (1) early onset, rapid progression or (2) late onset, slow progression.[4] The first type is considered to be the classic presentation, while the second type is the atypical presentation. Phenotypes of the different disorders appear to be dependent on age, i.e. amount of iron accumulation and cognitive ability.[5]


An effective treatment has yet to be found. In many cases electrical stimulation of the globus pallidus has been shown to produce improvement of dystonia severity, however it has not been shown to delay neurodegeneration.[5][6] There is often overlap in the phenotypes of the symptoms both between different NBIA disorders and between NBIA and other disorders, leading to misdiagnoses.[6] Treatments typically treat or ameliorate the symptoms and do not address the accumulation of iron.[6] Psychotherapy, such as dopaminergic drugs, anticholinergics, tetrabenazine, is often used to treat the symptoms but does not improve the long term outcome of the patient.[6]

The group includes the following disorders:


  1. ^ Bettencourt, C; Forabosco, P; Wiethoff, S; Heidari, M; Johnstone, DM; Botía, JA; Collingwood, JF; Hardy, J; Milward, EA; Ryten, M; Houlden, H; UK Brain Expression Consortium, (UKBEC) (17 December 2015). "Gene co-expression networks shed light into diseases of brain iron accumulation.". Neurobiology of disease. 87: 59–68. PMC 4731015Freely accessible. PMID 26707700. doi:10.1016/j.nbd.2015.12.004. 
  2. ^ Gregory, A.; Polster, B. J.; Hayflick, S. J. (2009-02-01). "Clinical and genetic delineation of neurodegeneration with brain iron accumulation". Journal of Medical Genetics. 46 (2): 73–80. ISSN 1468-6244. PMC 2675558Freely accessible. PMID 18981035. doi:10.1136/jmg.2008.061929. 
  3. ^ a b c d Dusek, Petr; Schneider, Susanne A. "Neurodegeneration with brain iron accumulation". Current Opinion in Neurology. 25 (4): 499–506. doi:10.1097/wco.0b013e3283550cac. 
  4. ^ a b Hayflick, S. J.; Hartman, M.; Coryell, J.; Gitschier, J.; Rowley, H. (2006-06-01). "Brain MRI in Neurodegeneration with Brain Iron Accumulation with and without PANK2 Mutations". American Journal of Neuroradiology. 27 (6): 1230–1233. ISSN 0195-6108. 
  5. ^ a b Schneider, Susanne A.; Bhatia, Kailash P. "Syndromes of Neurodegeneration With Brain Iron Accumulation". Seminars in Pediatric Neurology. 19 (2): 57–66. doi:10.1016/j.spen.2012.03.005. 
  6. ^ a b c d Schneider, Susanne A.; Dusek, Petr; Hardy, John; Westenberger, Ana; Jankovic, Joseph; Bhatia, Kailash P. (2013). "Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)". Current Neuropharmacology. 11: 59–79. doi:10.2174/157015913804999469.