Genetics and pathophysiology of neurodegeneration with brain iron accumulation (NBIA)

Current Neuropharmacology

Volumn 11, Issue 1, 2013, Pages 59-79

  Schneider, Susanne A ^a,b   Dusek, Petr ^c   Hardy, John ^b   Westenberger, Ana ^d   Jankovic, Joseph ^e   Bhatia, Kailash P ^b  

^a UNIVERSITY OF KIEL   (Germany)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c CHARLES UNIVERSITY   (Czech Republic)

^d UNIVERSITY OF LÜBECK   (Germany)

^e BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Ceramide; Dystonia; Iron; MPAN; NBIA; Parkinsonism; PKAN; PLA2G6

Indexed keywords

CERAMIDE; CERULOPLASMIN; DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; FATTY ACID AMIDASE; MITOCHONDRIAL PROTEIN; PANTOTHENATE KINASE; PHOSPHOLIPASE A2;

ABDOMINAL DISCOMFORT; AGRANULOCYTOSIS; ARTHRITIS; AUTOSOMAL RECESSIVE DISORDER; BRAIN DEPTH STIMULATION; CREATININE BLOOD LEVEL; DIARRHEA; EYE TOXICITY; GENE MUTATION; GENOTYPE; HEREDITY; HUMAN; IRON CHELATION; IRON METABOLISM; IRON OVERLOAD; LEUKODYSTROPHY; LEWY BODY; LIPOFUSCINOSIS; LUNG TOXICITY; NAUSEA; NEURODEGENERATION WITH BRAIN IRON ACCUMULATION; NEUROFIBRILLARY TANGLE; NEUTROPENIA; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PALLIDOTOMY; PARAPLEGIA; PHENOTYPE; RASH; REVIEW; SIDE EFFECT; SKIN MANIFESTATION; STOMACH PAIN; THALAMOTOMY;

EID: 84874928336     PISSN: 1570159X     EISSN: 18756190     Source Type: Journal    
DOI: 10.2174/157015913804999469     Document Type: Review

References (203)

1. Fleming RE; Ponka, P. Iron overload in human disease. N. Engl. J. Med., 2012, 366, 348-59.
2. Dusek, P.; Jankovic, J.; Weidong, L. Iron dysregulation in movement disorders. Neurobiol. Dis., 2012, 46, 1-18.
3. Schneider, S. A.; Hardy, J.; Bhatia, K. P. Syndromes of neurodegeneration with brain iron accumulation (NBIA): An update on clinical presentations, histological and genetic underpinnings, and treatment considerations. Mov. Disord., 2012, 27, 42-53.
4. Crichton, R. R.; Dexter, D. T.; Ward, R. J. Brain iron metabolism and its perturbation in neurological diseases. J. Neural. Transm., 2011, 118, 301-14.
5. Connor, J. R.; Menzies, S. L.; St Martin, S. M.; Mufson, E. J. Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains. J. Neurosci. Res., 1990, 27, 595-611.
6. Connor, J. R.; Menzies, S. L. Altered cellular distribution of iron in the central nervous system of myelin deficient rats. Neuroscience, 1990, 34, 265-71.
7. Schenck, J. F.; Zimmerman, E. A. High-field magnetic resonance imaging of brain iron: birth of a biomarker? NMR Biomed., 2004, 17, 433-45.
8. Taylor, E. M.; Morgan, E. H. Developmental changes in transferrin and iron uptake by the brain in the rat. Brain Res. Dev. Brain Res., 1990, 55, 35-42.
9. Zecca, L.; Gallorini, M.; Schunemann, V.; Trautwein, A. X.; Gerlach, M.; Riederer, P.; Vezzoni, P.; Tampellini, D. Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes. J. Neurochem., 2001, 76, 1766-73.
10. Todorich, B.; Pasquini, J. M.; Garcia, C. I.; Paez, P. M.; Connor, J. R. Oligodendrocytes and myelination: the role of iron. Glia, 2009, 57, 467-78.
11. Schenck, J. F.; Zimmermann, F. A. High-field magnetic resonance imaging of brain iron: birth of a biomarker? NMR Biomed., 2004, 17, 433-45.
12. Hallgren, B.; Sourander, P. The effect of age on the non-haemin iron in the1461 human brain. J. Neurochem., 1958, 3, 41-51.
13. Morris, C. M.; Candy, J. M.; Oakley, A. E.; Bloxham, C. A.; Edwardson, J. A. Histochemical distribution of non-haem iron in the human brain. Acta Anat (Basel)., 1992, 144, 235-57.
14. Drayer, B.; Burger, P.; Darwin, R.; Riederer, S.; Herfkens, R.; Johnson, G. A. MRI of brain iron. Am. J. Roentgenol., 1986, 147, 103-10.
15. Yao, B.; Li, T. Q.; Gelderen, P.; Shmueli, K.; de Zwart, J. A.; Duyn, J. H. Susceptibility contrast in high field MRI of human brain as a function of tissue iron content. Neuroimage, 2009, 44, 1259-66.
16. Pfefferbaum, A.; Adalsteinsson, E.; Rohlfing, T.; Sullivan, E. V. MRI estimates of brain iron concentration in normal aging: comparison of field-dependent (FDRI) and phase (SWI) methods. Neuroimage, 2009, 47, 493-500.
17. Farrall, A. J.; Wardlaw, J. M. Blood-brain barrier: ageing andmicrovascular disease-systematic review and meta-analysis. Neurobiol. Aging, 2009, 30, 337-52.
18. Faucheux, B. A.; Bonnet, A. M.; Agid, Y.; Hirsch, E. C. Blood vessels change in the mesencephalon of patients with Parkinson's disease. Lancet, 1999, 353, 981-2.
19. Matsunaga, T.; Kotamraju, S.; Kalivendi, S. V.; Dhanasekaran, A.; Joseph, J.; Kalyanaraman, B. Ceramide-induced intracellular oxidant formation, iron signaling, and apoptosis in endothelial cells: protective role of endogenous nitric oxide. J. Biol. Chem., 2004, 279, 28614-24.
20. Sastry, S.; Arendash, G. W. Time-dependent changes in iron levels and associated neuronal loss within the substantia nigra following lesions within the neostriatum/globus pallidus complex. Neuroscience, 1995, 67, 649-66.
21. Dwork, A. J.; Lawler, G.; Zybert, P. A.; Durkin, M.; Osman, M.; Willson, N.; Barkai, A. I. An autoradiographic study of the uptake and distribution of iron by the brain of the young rat. Brain Res., 1990, 518, 31-9.
22. Berlet, H. H.; Volk, B. Studies of human myelin proteins during old age. Mech. Ageing Dev., 1980, 14, 222.
23. Williams, R.; Buchheit, C. L.; Berman, N. E.; LeVine, S. M. Pathogenic implications of iron accumulation in multiple sclerosis. J. Neurochem., 2012, 120, 7-25.
24. Bagnato, F.; Hametner, S.; Yao, B.; van, G. P.; Merkle, H.; Cantor, F. K.; Lassmann, H.; Duyn, J. H. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain, 2011, 134, 3602-15.
25. Lee, D. W.; Andersen, J. K. Role of HIF-1 in iron regulation: potential therapeutic strategy for neurodegenerative disorders. Curr. Mol. Med., 2006, 6, 883-93.
26. Qi, Y.; Jamindar, T. M.; Dawson, G. Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes. J. Neurochem., 1995, 64, 2458-64.
27. Gutsaeva, D. R.; Carraway, M. S.; Suliman, H. B.; Demchenko, I. T.; Shitara, H.; Yonekawa, H.; Piantadosi, C. A. Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism. J. Neurosci., 2008, 28, 2015-24.
28. Cowen, D.; Olmstead, E. V. Infantile neuroaxonal dystrophy. J. Neuropathol. Exp. Neurol., 1963, 22, 175-236.
29. Hallervorden, J.; Spatz, H. Eigenartige Erkrankung im extrapyramidalen System mit besonderer Beteiligung des Globus pallidus und der Substantia nigra.: Ein Beitrag zu den Beziehungen zwischen diesen beiden Zentren. Z Ges Neurol. Psychiat., 1922, 254-302.
30. Stankiewicz, J.; Panter, S. S.; Neema, M.; Arora, A.; Batt, C. E.; Bakshi, R. Iron in chronic brain disorders: imaging and neurotherapeutic implications. Neurotherapeutics, 2007, 4, 371-86.
31. Zhang, J.; Zhang, Y.; Wang, J.; Cai, P.; Luo, C.; Qian, Z.; Dai, Y.; Feng, H. Characterizing iron deposition in Parkinson's disease using susceptibility-weighted imaging: an in vivo MR study. Brain Res., 2010, 1330, 124-30.
32. Rossi, M.; Ruottinen, H.; Elovaara, I.; Ryymin, P.; Soimakallio, S.; Eskola, H.; Dastidar, P. Brain iron deposition and sequence characteristics in Parkinsonism: comparison of SWI, T(2)* maps, T(2)-weighted-, and FLAIR-SPACE. Invest. Radiol., 2010, 45, 795-802.
33. Kell, D. B. Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples. Arch. Toxicol., 2010, 84, 825-89.
34. Hayflick, S. J. Neurodegeneration with brain iron accumulation: from genes to pathogenesis. Semin. Pediatr. Neurol., 2006, 13, 182-5.
35. Hayflick, S. J.; Westaway, S. K.; Levinson, B.; Zhou, B.; Johnson, M. A.; Ching, K. H.; Gitschier, J. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N. Engl. J. Med., 2003, 348, 33-40.
36. Schneider, S. A.; Aggarwal, A.; Bhatt, M.; Dupont, E.; Tisch, S.; Limousin, P.; Lee, P.; Quinn, N.; Bhatia, K. P. Severe tongue protrusion dystonia: clinical syndromes and possible treatment. Neurology, 2006, 67, 940-3.
37. Assami, S.; Azzedine, H.; Nouioua, S.; Mundwiller, E.; Mahoui, S.; Makri, S.; Djemai, M.; Grid, D.; Brice, A.; Hamadouche, T.; Stevanin, G.; Tazir, M. Pantothenate kinase-associated neurodegeneration: clinical description of 10 patients and identification of new mutations. Mov. Disord., 2011, 26, 1777-9.
38. Marelli, C.; Piacentini, S.; Garavaglia, B.; Girotti, F.; Albanese, A. Clinical and neuropsychological correlates in two brothers with pantothenate kinase-associated neurodegeneration. Mov. Disord., 2005, 20, 208-12.
39. Thomas, M.; Hayflick, S. J.; Jankovic, J. Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration. Mov. Disord., 2004, 19, 36-42.
40. Egan, R. A.; Weleber, R. G.; Hogarth, P.; Gregory, A.; Coryell, J.; Westaway, S. K.; Gitschier, J.; Das, S.; Hayflick, S. J. Neuroophthalmologic and electroretinographic findings in pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz syndrome). Am. J. Ophthalmol., 2005, 140, 267-74.
41. Bozi, M.; Matarin, M.; Theocharis, I.; Potagas, C.; Stefanis, L. A patient with pantothenate kinase-associated neurodegeneration and supranuclear gaze palsy. Clin. Neurol. Neurosurg., 2009, 111, 688-90.
42. Antonini, A.; Goldwurm, S.; Benti, R.; Prokisch, H.; Ebhardt, M.; Cilia, R.; Zini, M.; Righini, A.; Cossu, G.; Pezzoli, G. Genetic, clinical, and imaging characterization of one patient with lateonset, slowly progressive, pantothenate kinase-associated neurodegeneration. Mov. Disord., 2006, 21, 417-8.
43. Aggarwal, A.; Schneider, S. A.; Houlden, H.; Silverdale, M.; Paudel, R.; Paisan-Ruiz, C.; Desai, S.; Munshi, M.; Sanghvi, D.; Hardy, J.; Bhatia, K. P.; Bhatt, M. Indian-subcontinent NBIA: unusual phenotypes, novel PANK2 mutations, and undetermined genetic forms. Mov. Disord., 2010, 25, 1424-31.
44. Yoon, W. T.; Lee, W. Y.; Shin, H. Y.; Lee, S. T.; Ki, C. S. Novel PANK2 gene mutations in korean patient with pantothenate kinaseassociated neurodegeneration presenting unilateral dystonic tremor. Mov. Disord., 2010, 25, 245-7.
45. Chung, S. J.; Lee, J. H.; Lee, M. C.; Yoo, H. W.; Kim, G. H. Focal hand dystonia in a patient with PANK2 mutation. Mov. Disord., 2008, 23, 466-8.
46. Fantini, M. L.; Cossu, G.; Molari, A.; Cabinio, M.; Uyanik, O.; Cilia, R.; Melis, M.; Antonini, A.; Ferini-Strambi, L. Sleep in genetically confirmed pantothenate kinase-associated neurodegeneration: a video-polysomnographic study. Parkinsons Dis., 2010, 2010, 342834.
47. Delgado, R. F.; Sanchez, P. R.; Speckter, H.; Then, E. P.; Jimenez, R.; Oviedo, J.; Dellani, P. R.; Foerster, B.; Stoeter, P. Missense PANK2 mutation without "Eye of the tiger" sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN). J. Magn. Reson. Imaging, 2012, 35, 788-94.
48. Fermin-Delgado, R.; Roa-Sanchez, P.; Speckter, H.; Perez-Then, E.; Rivera-Mejia, D.; Foerster, B.; Stoeter, P. Involvement of Globus Pallidus and Midbrain Nuclei in Pantothenate Kinase-Associated Neurodegeneration: Measurement of T2 and T2* Time. Clin. Neuroradiol., 2012, (epub ehead of print).
49. Hayflick, S. J.; Hartman, M.; Coryell, J.; Gitschier, J.; Rowley, H. Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. Am. J. Neuroradiol., 2006, 27, 1230-3.
50. Hayflick, S. J.; Penzien, J. M.; Michl, W.; Sharif, U. M.; Rosman, N. P.; Wheeler, P. G. Cranial MRI changes may precede symptoms in Hallervorden-Spatz syndrome. Pediatr. Neurol., 2001, 25, 166-9.
51. Chiapparini, L.; Savoiardo, M.; D'Arrigo, S.; Reale, C.; Zorzi, G.; Zibordi, F.; Cordelli, D. M.; Franzoni, E.; Garavaglia, B.; Nardocci, N. The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration. Neuropediatrics, 2011, 42, 159-62.
52. Grandas, F.; Fernandez-Carballal, C.; Guzman-de-Villoria, J.; Ampuero, I. Treatment of a dystonic storm with pallidal stimulation in a patient with PANK2 mutation. Mov. Disord., 2011, 26, 921-2.
53. Schneider, S. A.; Hardy, J.; Bhatia, K. P. Iron Accumulation in Syndromes of Neurodegeneration with Brain Accumulation-causative or consequential? J. Neurol. Neurosurg. Psychiatry, 2009, 80, 589-90.
54. Awasthi, R.; Gupta, R. K.; Trivedi, R.; Singh, J. K.; Paliwal, V. K.; Rathore, R. K. Diffusion tensor MR imaging in children with pantothenate kinase-associated neurodegeneration with brain iron accumulation and their siblings. Am. J. Neuroradiol., 2010, 31, 442-7.
55. Hajek, M.; Adamovicova, M.; Herynek, V.; Skoch, A.; Jiru, F.; Krepelova, A.; Dezortova, M. MR relaxometry and 1H MR spectroscopy for the determination of iron and metabolite concentrations in PKAN patients. Eur. Radiol., 2005, 15, 1060-8.
56. Cossu, G.; Cella, C.; Melis, M.; Antonini, A.; Floris, G. L.; Ruffini, L.; Spissu, A. [123I]FP-CIT SPECT findings in two patients with Hallervorden-Spatz disease with homozygous mutation in PANK2 gene. Neurology, 2005, 64, 167-8.
57. Hermann, W.; Barthel, H.; Reuter, M.; Georgi, P.; Dietrich, J.; Wagner, A. [Hallervorden-Spatz disease: findings in the nigrostriatal system]. Nervenarzt., 2000, 71, 660-5.
58. Hartig, M. B.; Hortnagel, K.; Garavaglia, B.; Zorzi, G.; Kmiec, T.; Klopstock, T.; Rostasy, K.; Svetel, M.; Kostic, V. S.; Schuelke, M.; Botz, E.; Weindl, A.; Novakovic, I.; Nardocci, N.; Prokisch, H.; Meitinger, T. Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Ann. Neurol., 2006, 59, 248-56.
59. McNeill, A.; Birchall, D.; Hayflick, S. J.; Gregory, A.; Schenk, J. F.; Zimmerman, E. A.; Shang, H.; Miyajima, H.; Chinnery, P. F. T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology, 2008, 70, 1614-9.
60. Seo, J. H.; Song, S. K.; Lee, P. H. A Novel PANK2 Mutation in a Patient with Atypical Pantothenate-Kinase-Associated Neurodegeneration Presenting with Adult-Onset Parkinsonism. J. Clin. Neurol., 2009, 5, 192-4.
61. Mak, C. M.; Sheng, B.; Lee, H. H.; Lau, K. K.; Chan, W. T.; Lam, C. W.; Chan, Y. W. Young-onset parkinsonism in a Hong Kong Chinese man with adult-onset Hallervorden-Spatz syndrome. Int. J. Neurosci., 2011, 121, 224-7.
62. Doi, H.; Koyano, S.; Miyatake, S.; Matsumoto, N.; Kameda, T.; Tomita, A.; Miyaji, Y.; Suzuki, Y.; Sawaishi, Y.; Kuroiwa, Y. Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: clinical features and (99m)Tc-ECD brain perfusion SPECT findings. J. Neurol. Sci., 2010, 290, 172-6.
63. Kostic, V. S.; Svetel, M.; Mijajlovic, M.; Pavlovic, A.; Jecmenica-Lukic, M.; Kozic, D. Transcranial sonography in pantothenate kinase-associated neurodegeneration. J. Neurol., 2012, 259, 959-65.
64. Liman, J.; Wellmer, A.; Rostasy, K.; Bahr, M.; Kermer, P. Transcranial ultrasound in neurodegeneration with brain iron accumulation (NBIA). Eur. J. Paediatr. Neurol., 2012, 16, 175-8.
65. Kruer, M. C.; Hiken, M.; Gregory, A.; Malandrini, A.; Clark, D.; Hogarth, P.; Grafe, M.; Hayflick, S. J.; Woltjer, R. L. Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration. Brain, 2011, 134, 947-58.
66. Saito, Y.; Kawai, M.; Inoue, K.; Sasaki, R.; Arai, H.; Nanba, E.; Kuzuhara, S.; Ihara, Y.; Kanazawa, I.; Murayama, S. Widespread expression of alpha-synuclein and tau immunoreactivity in Hallervorden-Spatz syndrome with protracted clinical course. J. Neurol. Sci., 2000, 177, 48-59.
67. Wakabayashi, K.; Fukushima, T.; Koide, R.; Horikawa, Y.; Hasegawa, M.; Watanabe, Y.; Noda, T.; Eguchi, I.; Morita, T.; Yoshimoto, M.; Iwatsubo, T.; Takahashi, H. Juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease) with diffuse neurofibrillary and lewy body pathology. Acta Neuropathol., 2000, 99, 331-6.
68. Neumann, M.; Adler, S.; Schluter, O.; Kremmer, E.; Benecke, R.; Kretzschmar, H. A. Alpha-synuclein accumulation in a case of neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome) with widespread cortical and brainstem-type Lewy bodies. Acta Neuropathol., 2000, 100, 568-74.
69. Galvin, J. E.; Giasson, B.; Hurtig, H. I.; Lee, V. M.; Trojanowski, J. Q. Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology. Am. J. Pathol., 2000, 157, 361-8.
70. Williamson, K.; Sima, A. A.; Curry, B.; Ludwin, S. K. Neuroaxonal dystrophy in young adults: a clinicopathological study of two unrelated cases. Ann. Neurol., 1982, 11, 335-43.
71. Eidelberg, D.; Sotrel, A.; Joachim, C.; Selkoe, D.; Forman, A.; Pendlebury, W. W.; Perl, D. P. Adult onset Hallervorden-Spatz disease with neurofibrillary pathology. A discrete clinicopathological entity. Brain, 1987, 110 (Pt 4), 993-1013.
72. Kotzbauer, P. T.; Truax, A. C.; Trojanowski, J. Q.; Lee, V. M. Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. J. Neurosci., 2005, 25, 689-98.
73. Lin, M. T.; Beal, M. F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006, 443, 787-95.
74. Leoni, V.; Strittmatter, L.; Zorzi, G.; Zibordi, F.; Dusi, S.; Garavaglia, B.; Venco, P.; Caccia, C.; Souza, A. L.; Deik, A.; Clish, C. B.; Rimoldi, M.; Ciusani, E.; Bertini, E.; Nardocci, N.; Mootha, V. K.; Tiranti, V. Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations. Mol. Genet. Metab., 2012, 105, 463-71.
75. Poli, M.; Derosas, M.; Luscieti, S.; Cavadini, P.; Campanella, A.; Verardi, R.; Finazzi, D.; Arosio, P. Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron deregulation. Neurobiol. Dis., 2010, 39, 204-10.
76. Castelnau, P.; Cif, L.; Valente, E. M.; Vayssiere, N.; Hemm, S.; Gannau, A.; DiGiorgio, A.; Coubes, P. Pallidal stimulation improves pantothenate kinase-associated neurodegeneration. Ann. Neurol., 2005, 57, 738-41.
77. Mikati, M. A.; Yehya, A.; Darwish, H.; Karam, P.; Comair, Y. Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration. Eur. J. Paediatr. Neurol., 2009, 13, 61-4.
78. Krause, M.; Fogel, W.; Tronnier, V.; Pohle, S.; Hortnagel, K.; Thyen, U.; Volkmann, J. Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinaseassociated neurodegeneration. Mov. Disord., 2006, 21, 2255-7.
79. Szumowski, J.; Bas, E.; Gaarder, K.; Schwarz, E.; Erdogmus, D.; Hayflick, S. Measurement of brain iron distribution in Hallevorden-Spatz syndrome. J. Magn. Reson. Imaging, 2010, 31, 482-9.
80. Tsukamoto, H.; Inui, K.; Taniike, M.; Nishimoto, J.; Midorikawa, M.; Yoshimine, T.; Kato, A.; Ikeda, T.; Hayakawa, T.; Okada, S. A case of Hallervorden-Spatz disease: progressive and intractable dystonia controlled by bilateral thalamotomy. Brain Dev., 1992, 14, 269-72.
81. Balas, I.; Kovacs, N.; Hollody, K. Staged bilateral stereotactic pallidothalamotomy for life-threatening dystonia in a child with Hallervorden-Spatz disease. Mov. Disord., 2006, 21, 82-5.
82. Kyriagis, M.; Grattan-Smith, P.; Scheinberg, A.; Teo, C.; Nakaji, N.; Waugh, M. Status dystonicus and Hallervorden-Spatz disease: treatment with intrathecal baclofen and pallidotomy. J. Paediatr. Child Health, 2004, 40, 322-5.
83. Justesen, C. R.; Penn, R. D.; Kroin, J. S.; Egel, R. T. Stereotactic pallidotomy in a child with Hallervorden-Spatz disease. Case report. J. Neurosurg., 1999, 90, 551-4.
84. Ostrem, J. L.; Marks, W. J., Jr.; Volz, M. M.; Heath, S. L.; Starr, P. A. Pallidal deep brain stimulation in patients with cranial-cervical dystonia (Meige syndrome). Mov. Disord., 2007, 22, 1885-91.
85. Speelman, J. D.; Contarino, M. F.; Schuurman, P. R.; Tijssen, M. A.; de Bie, R. M. Deep brain stimulation for dystonia: patient selection and outcomes. Eur. J. Neurol., 2010, 17 Suppl 1, 102-6.
86. Kupsch, A.; Kuehn, A.; Klaffke, S.; Meissner, W.; Harnack, D.; Winter, C.; Haelbig, T. D.; Kivi, A.; Arnold, G.; Einhaupl, K. M.; Schneider, G. H.; Trottenberg, T. Deep brain stimulation in dystonia. J. Neurol., 2003, 250 Suppl 1, I47-I52.
87. Timmermann, L.; Pauls, K. A.; Wieland, K.; Jech, R.; Kurlemann, G.; Sharma, N.; Gill, S. S.; Haenggeli, C. A.; Hayflick, S. J.; Hogarth, P.; Leenders, K. L.; Limousin, P.; Malanga, C. J.; Moro, E.; Ostrem, J. L.; Revilla, F. J.; Santens, P.; Schnitzler, A.; Tisch, S.; Valldeoriola, F.; Vesper, J.; Volkmann, J.; Woitalla, D.; Peker, S. Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation. Brain, 2010, 133, 701-12.
88. Adamovicova, M.; Jech, R.; Urgosik, D.; Spackova, N.; Krepelova, A. Pallidal stimulation in siblings with pantothenate kinaseassociated neurodegeneration: four-year follow-up. Mov. Disord., 2011, 26, 184-7.
89. Lim, B. C.; Ki, C. S.; Cho, A.; Hwang, H.; Kim, K. J.; Hwang, Y. S.; Kim, Y. E.; Yun, J. Y.; Jeon, B. S.; Lim, Y. H.; Paek, S. H.; Chae, J. H. Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation. Eur. J. Neurol., 2011.
90. Mahoney, R.; Selway, R.; Lin, J. P. Cognitive functioning in children with pantothenate-kinase-associated neurodegeneration undergoing deep brain stimulation. Dev. Med. Child. Neurol., 2011, 53, 275-9.
91. Mylius, V.; Gerstner, A.; Peters, M.; Prokisch, H.; Leonhardt, A.; Hellwig, D.; Rosenow, F. Low-frequency rTMS of the premotor cortex reduces complex movement patterns in a patient with pantothenate kinase-associated neurodegenerative disease (PKAN). Neurophysiol. Clin., 2009, 39, 27-30.
92. Rana, A.; Seinen, E.; Siudeja, K.; Muntendam, R.; Srinivasan, B.; van der Want, J. J.; Hayflick, S.; Reijngoud, D. J.; Kayser, O.; Sibon, O. C. Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration. Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 6988-93.
93. Wu, Z.; Li, C.; Lv, S.; Zhou, B. Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model. Hum. Mol. Genet., 2009, 18, 3659-72.
94. Morgan, N. V.; Westaway, S. K.; Morton, J. E.; Gregory, A.; Gissen, P.; Sonek, S.; Cangul, H.; Coryell, J.; Canham, N.; Nardocci, N.; Zorzi, G.; Pasha, S.; Rodriguez, D.; Desguerre, I.; Mubaidin, A.; Bertini, E.; Trembath, R. C.; Simonati, A.; Schanen, C.; Johnson, C. A.; Levinson, B.; Woods, C. G.; Wilmot, B.; Kramer, P.; Gitschier, J.; Maher, E. R.; Hayflick, S. J. PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. Nat. Genet., 2006, 38, 752-4.
95. Paisan-Ruiz, C.; Bhatia, K. P.; Li, A.; Hernandez, D.; Davis, M.; Wood, N. W.; Hardy, J.; Houlden, H.; Singleton, A.; Schneider, S. A. Characterization of PLA2G6 as a locus for dystoniaparkinsonism. Ann. Neurol., 2009, 65, 19-23.
96. Deng, H.; Liang, H.; Jankovic, J. The F-box only protein 7 gene in parkinsonian-pyramidal disease. Arch. Neurol., 2012, (in press).
97. Kurian, M. A.; Morgan, N. V.; MacPherson, L.; Foster, K.; Peake, D.; Gupta, R.; Philip, S. G.; Hendriksz, C.; Morton, J. E.; Kingston, H. M.; Rosser, E. M.; Wassmer, E.; Gissen, P.; Maher, E. R. Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). Neurology, 2008, 70, 1623-9.
98. Gregory, A.; Polster, B. J.; Hayflick, S. J. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J. Med. Genet., 2009, 46, 73-80.
99. Paisan-Ruiz, C.; Li, A.; Schneider, S. A.; Holton, J. L.; Johnson, R.; Kidd, D.; Chataway, J.; Bhatia, K. P.; Lees, A. J.; Hardy, J.; Revesz, T.; Houlden, H. Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. Neurobiol. Aging, 2012, 33, 814-23.
100. Malik, I.; Turk, J.; Mancuso, D. J.; Montier, L.; Wohltmann, M.; Wozniak, D. F.; Schmidt, R. E.; Gross, R. W.; Kotzbauer, P. T. Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy caused by PLA2G6 mutations. Am. J. Pathol., 2008, 172, 406-16.
101. Adibhatla, R. M.; Hatcher, J. F. Phospholipase A(2): reactive oxygen species, and lipid peroxidation in CNS pathologies. BMB Rep., 2008, 41, 560-7.
102. Adibhatla, R. M.; Hatcher, J. F. Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal., 2010, 12, 125-69.
103. Engel, L. A.; Jing, Z.; O'Brien, D. E.; Sun, M.; Kotzbauer, P. T. Catalytic function of PLA2G6 is impaired by mutations associated with Infantile Neuroaxonal Dystrophy but not Dystonia-Parkinsonism. PLoS ONE., 2011, 5, e12897.
104. H. Vinters, M. Farrell, P. Mischel, K. Anders, Diagnostic Neuropathology. 1998 (Marcel Dekker Incorporated: New York, NY, U.S.A.).
105. Gregory, A.; Westaway, S. K.; Holm, I. E.; Kotzbauer, P. T.; Hogarth, P.; Sonek, S.; Coryell, J. C.; Nguyen, T. M.; Nardocci, N.; Zorzi, G.; Rodriguez, D.; Desguerre, I.; Bertini, E.; Simonati, A.; Levinson, B.; Dias, C.; Barbot, C.; Carrilho, I.; Santos, M.; Malik, I.; Gitschier, J.; Hayflick, S. J. Neurodegeneration associated with genetic defects in phospholipase A(2). Neurology, 2008, 71, 1402-9.
106. Kruer, M. C.; Paisan-Ruiz, C.; Boddaert, N.; Yoon, B. S.; Hama, H.; Gregory, A.; Malandrini, A.; Woltjer, R. L.; Munnich, A.; Gobin, S.; Polster, B. J.; Palmeri, S.; Edvardson, S.; Hardy, J.; Houlden, H.; Hayflick, S. Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA). Ann. Neurol., 2010, 68, 611-8.
107. Schneider, S. A.; Bhatia, K. P. Three faces of the same gene: FA2H links neurodegeneration with brain iron accumulation, leukodystrophies, and hereditary spastic paraplegias. Ann. Neurol., 2010, 68, 575-7.
108. Dick, K. J.; Eckhardt, M.; Paisan-Ruiz, C.; Alshehhi, A. A.; Proukakis, C.; Sibtain, N. A.; Maier, H.; Sharifi, R.; Patton, M. A.; Bashir, W.; Koul, R.; Raeburn, S.; Gieselmann, V.; Houlden, H.; Crosby, A. H. Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). Hum. Mutat., 2010, 31, E1251-E1260.
109. Edvardson, S.; Hama, H.; Shaag, A.; Gomori, J. M.; Berger, I.; Soffer, D.; Korman, S. H.; Taustein, I.; Saada, A.; Elpeleg, O. Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. Am. J. Hum. Genet., 2008, 83, 643-8.
110. Garone, C.; Pippucci, T.; Cordelli, D. M.; Zuntini, R.; Castegnaro, G.; Marconi, C.; Graziano, C.; Marchiani, V.; Verrotti, A.; Seri, M.; Franzoni, E. FA2H-related disorders: a novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype. Dev. Med. Child Neurol., 2011.
111. Pierson, T. M.; Simeonov, D. R.; Sincan, M.; Adams, D. A.; Markello, T.; Golas, G.; Fuentes-Fajardo, K.; Hansen, N. F.; Cherukuri, P. F.; Cruz, P.; Blackstone, C.; Tifft, C.; Boerkoel, C. F.; Gahl, W. A. Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. Eur. J. Hum. Genet., 2012, 20, 476-9.
112. Bras, J.; Singleton, A.; Cookson, M. R.; Hardy, J. Potential role of ceramide metabolism in Lewy body disease. Eur. J. Biochem. (FEBS)., 2008, 275, 5767-73.
113. Hourani, R.; El-Hajj, T.; Barada, W. H.; Hourani, M.; Yamout, B. I. MR imaging findings in autosomal recessive hereditary spastic paraplegia. Am. J. Neuroradiol., 2009, 30, 936-40.
114. Kang, S. Y.; Lee, M. H.; Lee, S. K.; Sohn, Y. H. Levodoparesponsive parkinsonism in hereditary spastic paraplegia with thin corpus callosum. Parkinsonism Relat. Disord., 2004, 10, 425-7.
115. Micheli, F.; Cersosimo, M. G.; Zuniga, R. C. Hereditary spastic paraplegia associated with dopa-responsive parkinsonism. Mov. Disord., 2006, 21, 716-7.
116. Schicks, J., Synofzik, M., Petrusson, H., Bauer, P., and Schöls, L. Juvenile parkinsonism due to a novel SPG15 mutation. Mov. Disord., 25[S2], S524. 2010. Ref Type: Abstract
117. Anheim, M.; Lagier-Tourenne, C.; Stevanin, G.; Fleury, M.; Durr, A.; Namer, I. J.; Denora, P.; Brice, A.; Mandel, J. L.; Koenig, M.; Tranchant, C. SPG11 spastic paraplegia. A new cause of juvenile parkinsonism. J. Neurol., 2009, 256, 104-8.
118. White, K. D.; Ince, P. G.; Lusher, M.; Lindsey, J.; Cookson, M.; Bashir, R.; Shaw, P. J.; Bushby, K. M. Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation. Neurology, 2000, 55, 89-94.
119. Potter, K. A.; Kern, M. J.; Fullbright, G.; Bielawski, J.; Scherer, S. S.; Yum, S. W.; Li, J. J.; Cheng, H.; Han, X.; Venkata, J. K.; Kbar Ali, K. P.; Rohrer, B.; Hama, H. Central nervous system dysfunction in a mouse model of Fa2h deficiency. Glia, 2011, 59, 1009-21.
120. Zoller, I.; Meixner, M.; Hartmann, D.; Bussow, H.; Meyer, R.; Gieselmann, V.; Eckhardt, M. Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration. J. Neurosci., 2008, 28, 9741-54.
121. Hartig, M. B.; Iuso, A.; Haack, T.; Kmiec, T.; Jurkiewicz, E.; Heim, K.; Roeber, S.; Tarabin, V.; Dusi, S.; Krajewska-Walasek, M.; Jozwiak, S.; Hempel, M.; Winkelmann, J.; Elstner, M.; Oexle, K.; Klopstock, T.; Mueller-Felber, W.; Gasser, T.; Trenkwalder, C.; Tiranti, V.; Kretzschmar, H.; Schmitz, G.; Strom, T. M.; Meitinger, T.; Prokisch, H. Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am. J. Hum. Genet., 2011, 89, 543-50.
122. Horvath, R.; Holinski-Feder, E.; Neeve, V.; Neeve, V.; Pyle, A.; Griffin, H.; Ashok, D.; Foley, C.; Hudson, G.; Rautenstrauss, B.; Nürnberg, G.; Nürnberg, P.; Kortler, J.; Neitzel, B.; Bässmann, I.; Rahman, T.; Keavney, B.; Loughlin, J.; Hambleton, S.; Schoser, B.; Lochmüller, H.; Santibanez-Koref, M.; Chinnery, P. F. A new phenotype of brain iron accumulation with dystonia, optic atrophy and peripheral neuropathy. Mov. Disord., 2012, 27, 789-93.
123. Byrne, S.; Elamin, M.; Bede, P.; Shatunov, A.; Walsh, C.; Corr, B.; Heverin, M.; Jordan, N.; Kenna, K.; Lynch, C.; McLaughlin, R. L.; Iyer, P. M.; O'Brien, C.; Phukan, J.; Wynne, B.; Bokde, A. L.; Bradley, D.; Pender, N.; Al-Chalabi, A.; Hardiman, O. Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study. Lancet Neurol., 2012, 11, 232-40.
124. Snowden, J. S.; Rollinson, S.; Thompson, J. C.; Harris, J.; Stopford, C. L.; Richardson, A. M.; Jones, M.; Gerhard, A.; Davidson, Y. S.; Robinson, A.; Gibbons, A.; Hu, Q.; DuPlessis, D.; Neary, D.; Mann, D. M.; Pickering-Brown, S. M. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain, 2012, 135, 693-708.
125. Hsiung, G. Y.; Dejesus-Hernandez, M.; Feldman, H. H.; Sengdy, P.; Bouchard-Kerr, P.; Dwosh, E.; Butler, R.; Leung, B.; Fok, A.; Rutherford, N. J.; Baker, M.; Rademakers, R.; Mackenzie, I. R. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain, 2012, 135, 709-22.
126. Najim al-Din, A. S.; Wriekat, A.; Mubaidin, A.; Dasouki, M.; Hiari, M. Pallido-pyramidal degeneration, supranuclear upgaze paresis and dementia: Kufor-Rakeb syndrome. Acta Neurol. Scand., 1994, 89, 347-52.
127. Ramirez, A.; Heimbach, A.; Grundemann, J.; Stiller, B.; Hampshire, D.; Cid, L. P.; Goebel, I.; Mubaidin, A. F.; Wriekat, A. L.; Roeper, J.; Al Din, A.; Hillmer, A. M.; Karsak, M.; Liss, B.; Woods, C. G.; Behrens, M. I.; Kubisch, C. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat. Genet., 2006, 38, 1184-91.
128. Machner, B.; Sprenger, A.; Behrens, M. I.; Ramirez, A.; Bruggemann, N.; Klein, C.; Helmchen, C. Eye movement disorders in ATP13A2 mutation carriers (PARK9). Mov. Disord., 2010, 25, 2687-9.
129. Di Fonzo, A.; Chien, H. F.; Socal, M.; Giraudo, S.; Tassorelli, C.; Iliceto, G.; Fabbrini, G.; Marconi, R.; Fincati, E.; Abbruzzese, G.; Marini, P.; Squitieri, F.; Horstink, M. W.; Montagna, P.; Libera, A. D.; Stocchi, F.; Goldwurm, S.; Ferreira, J. J.; Meco, G.; Martignoni, E.; Lopiano, L.; Jardim, L. B.; Oostra, B. A.; Barbosa, E. R.; Bonifati, V. ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease. Neurology, 2007, 68, 1557-62.
130. Williams, D. R.; Hadeed, A.; Al Din, A. S.; Wreikat, A. L.; Lees, A. J. Kufor Rakeb disease: autosomal recessive, levodopa-responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia. Mov. Disord., 2005, 20, 1264-71.
131. Behrens, M. I.; Bruggemann, N.; Chana, P.; Venegas, P.; Kagi, M.; Parrao, T.; Orellana, P.; Garrido, C.; Rojas, C. V.; Hauke, J.; Hahnen, E.; Gonzalez, R.; Seleme, N.; Fernandez, V.; Schmidt, A.; Binkofski, F.; Kompf, D.; Kubisch, C.; Hagenah, J.; Klein, C.; Ramirez, A. Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Mov. Disord., 2010, 25, 1929-37.
132. Schneider, S. A.; Paisan-Ruiz, C.; Quinn, N. P.; Lees, A. J.; Houlden, H.; Hardy, J.; Bhatia, K. P. ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. Mov. Disord., 2010, 25, 979-84.
133. Bruggemann, N.; Hagenah, J.; Reetz, K.; Schmidt, A.; Kasten, M.; Buchmann, I.; Eckerle, S.; Bahre, M.; Munchau, A.; Djarmati, A.; van, d., V; Siebner, H.; Binkofski, F.; Ramirez, A.; Behrens, M. I.; Klein, C. Recessively inherited parkinsonism: effect of ATP13A2 mutations on the clinical and neuroimaging phenotype. Arch. Neurol., 2010, 67, 1357-63.
134. Chien, H. F.; Bonifati, V.; Barbosa, E. R. ATP13A2-related neurodegeneration (PARK9) without evidence of brain iron accumulation. Mov. Disord., 2011, 26, 1364-5.
135. Zittel, S.; Kroeger, J.; van, d., V; Siebner, H. R.; Bruggemann, N.; Ramirez, A.; Behrens, M. I.; Gerloff, C.; Baumer, T.; Klein, C.; Munchau, A. Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study. Parkinsonism Relat. Disord., 2012, 18, 590-4.
136. Paisan-Ruiz, C.; Guevara, R.; Federoff, M.; Hanagasi, H.; Sina, F.; Elahi, E.; Schneider, S. A.; Schwingenschuh, P.; Bajaj, N.; Emre, M.; Singleton, A. B.; Hardy, J.; Bhatia, K. P.; Brandner, S.; Lees, A. J.; Houlden, H. Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations. Mov. Disord., 2010, 25, 1791-800.
137. Park, J. S.; Mehta, P.; Cooper, A. A.; Veivers, D.; Heimbach, A.; Stiller, B.; Kubisch, C.; Fung, V. S.; Krainc, D.; kay-Sim, A.; Sue, C. M. Pathogenic effects of novel mutations in the P-type ATPase ATP13A2 (PARK9) causing Kufor-Rakeb syndrome, a form of early-onset Parkinsonism. Hum. Mutat., 2011.
138. Gusdon, A. M.; Zhu, J.; Van Houten, B.; Chu, C. T. ATP13A2 regulates mitochondrial bioenergetics through macroautophagy. Neurobiol. Dis., 2012, 45, 962-972.
139. Gruenewald, A.; Arns, B.; Seibler, P.; Rakovic, A.; Munchau, A.; Ramirez, A.; Sue, C. M.; Klein, C. ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome. Neurobiol. Aging., 2012.
140. Kurz, T.; Eaton, J. W.; Brunk, U. T. The role of lysosomes in iron metabolism and recycling. Int. J. Biochem. Cell Biol., 2011, 43, 1686-97.
141. De Volder, A. G.; Cirelli, S.; de Barsy, T.; Brucher, J. M.; Bol, A.; Michel, C.; Goiffinet, A. M. Neuronal ceroid-lipofuscinosis: preferential metabolic alterations in thalamus and posterior association cortex demonstrated by PET. J. Neurol. Neurosurg. Psychiatry, 1990, 53, 1063-7.
142. Tome, F. M.; Brunet, P.; Fardeau, M.; Hentati, F.; Reix, J. Familial disorder of the central and peripheral nervous systems with particular cytoplasmic lamellated inclusions in peripheral nerves, muscle satellite cells, and blood capillaries. Acta Neuropathol., 1985, 68, 209-17.
143. Carlier, G.; Dubru, J. M. Familial juvenile Parkinsonism. Acta Psychiatr. Belg., 1979, 32, 123-7.
144. Bras, J.; Verloes, A.; Schneider, S. A.; Mole, S. E.; Guerreiro, R. Mutation of the Parkinsonism Gene ATP13A2 Causes NeuronaCeroid-Lipofuscinosis. Hum. Mol. Genet., 2012, 21, 2646-50. l
145. Schreiner, R.; Becker, I.; Wiegand, M. H. [Kufs-disease; a rare cause of early-onset dementia]. Nervenarzt., 2000, 71, 411-5.
146. Galatioto, S.; Serra, S.; Di, P. R.; Cavallari, V.; Villari, D.; Musolino, R. A case of Kufs disease with abnormal pallidonigral iron deposit. Ital. J. Neurol. Sci., 1985, 6, 225-31.
147. Farias, F. H.; Zeng, R.; Johnson, G. S.; Wininger, F. A.; Taylor, J. F.; Schnabel, R. D.; McKay, S. D.; Sanders, D. N.; Lohi, H.; Seppala, E. H.; Wade, C. M.; Lindblad-Toh, K.; O'Brien, D. P.; Katz, M. L. A truncating mutation in ATP13A2 is responsible for adult-onset neuronal ceroid lipofuscinosis in Tibetan terriers. Neurobiol. Dis., 2011, 42, 468-74.
148. Wohlke, A.; Philipp, U.; Bock, P.; Beineke, A.; Lichtner, P.; Meitinger, T.; Distl, O. A one base pair deletion in the canine ATP13A2 gene causes exon skipping and late-onset neuronal ceroid lipofuscinosis in the Tibetan terrier. PLoS Genet., 2011, 7, e1002304.
149. McNeill, A.; Pandolfo, M.; Kuhn, J.; Shang, H.; Miyajima, H. The neurological presentation of ceruloplasmin gene mutations. Eur. Neurol., 2008, 60, 200-5.
150. Wolkow, N.; Song, Y.; Wu, T. D.; Qian, J.; Guerguin-Kern, J. L.; Dunaief, J. L. Aceruloplasminemia: retinal histopathologic manifestations and iron-mediated melanosome degradation. Arch. Ophthalmol., 2011, 129, 1466-74.
151. Gonzalez-Cuyar, L. F.; Perry, G.; Miyajima, H.; Atwood, C. S.; Riveros-Angel, M.; Lyons, P. F.; Siedlak, S. L.; Smith, M. A.; Castellani, R. J. Redox active iron accumulation in aceruloplasminemia. Neuropathology, 2008, 28, 466-71.
152. Kaneko, K.; Hineno, A.; Yoshida, K.; Ohara, S.; Morita, H.; Ikeda, S. Extensive brain pathology in a patient with aceruloplasminemia with a prolonged duration of illness. Hum. Pathol., 2012, 43, 451-6.
153. Oide, T.; Yoshida, K.; Kaneko, K.; Ohta, M.; Arima, K. Iron overload and antioxidative role of perivascular astrocytes in aceruloplasminemia. Neuropathol. Appl. Neurobiol., 2006, 32, 170-6.
154. Miyajima, H.; Takahashi, Y.; Kono, S. Aceruloplasminemia, an inherited disorder of iron metabolism. Biometals, 2003, 16, 205-13.
155. Yoshida, K.; Kaneko, K.; Miyajima, H.; Tokuda, T.; Nakamura, A.; Kato, M.; Ikeda, S. Increased lipid peroxidation in the brains of aceruloplasminemia patients. J. Neurol. Sci., 2000, 175, 91-5.
156. Mariani, R.; Arosio, C.; Pelucchi, S.; Grisoli, M.; Piga, A.; Trombini, P.; Piperno, A. Iron chelation therapy in aceruloplasminaemia: study of a patient with a novel missense mutation. Gut, 2004, 53, 756-8.
157. Daimon, M.; Susa, S.; Ohizumi, T.; Moriai, S.; Kawanami, T.; Hirata, A.; Yamaguchi, H.; Ohnuma, H.; Igarashi, M.; Kato, T. A novel mutation of the ceruloplasmin gene in a patient with heteroallelic ceruloplasmin gene mutation (HypoCPGM). Tohoku. J. Exp. Med., 2000, 191, 119-25.
158. Miyajima, H.; Kono, S.; Takahashi, Y.; Sugimoto, M.; Sakamoto, M.; Sakai, N. Cerebellar ataxia associated with heteroallelic ceruloplasmin gene mutation. Neurology, 2001, 57, 2205-10.
159. Keogh, M. J.; Jonas, P.; Coulthard, A.; Chinnery, P. F.; Burn, J. Neuroferritinopathy: a new inborn error of iron metabolism. Neurogenetics., 2012, 13, 93-6.
160. Chinnery, P. F.; Curtis, A. R.; Fey, C.; Coulthard, A.; Crompton, D.; Curtis, A.; Lombes, A.; Burn, J. Neuroferritinopathy in a French family with late onset dominant dystonia. J. Med. Genet., 2003, 40, e69.
161. Chinnery, P. F.; Crompton, D. E.; Birchall, D.; Jackson, M. J.; Coulthard, A.; Lombes, A.; Quinn, N.; Wills, A.; Fletcher, N.; Mottershead, J. P.; Cooper, P.; Kellett, M.; Bates, D.; Burn, J. Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation. Brain, 2007, 130, 110-9.
162. Kubota, A.; Hida, A.; Ichikawa, Y.; Momose, Y.; Goto, J.; Igeta, Y.; Hashida, H.; Yoshida, K.; Ikeda, S. I.; Kanazawa, I.; Tsuji, S. A novel ferritin light chain gene mutation in a Japanese family with neuroferritinopathy: Description of clinical features and implications for genotype-phenotype correlations. Mov. Disord., 2009, 24, 441-5.
163. Devos, D.; Tchofo, P. J.; Vuillaume, I.; Destee, A.; Batey, S.; Burn, J.; Chinnery, P. F. Clinical features and natural history of neuroferritinopathy caused by the 458dupA FTL mutation. Brain, 2009, 132, e109.
164. Ondo, W. G.; Adam, O. R.; Jankovic, J.; Chinnery, P. F. Dramatic response of facial stereotype/tic to tetrabenazine in the first reported cases of neuroferritinopathy in the United States. Mov. Disord., 2010, 25, 2470-2.
165. Vidal, R.; Ghetti, B.; Takao, M.; Brefel-Courbon, C.; Uro-Coste, E.; Glazier, B. S.; Siani, V.; Benson, M. D.; Calvas, P.; Miravalle, L.; Rascol, O.; Delisle, M. B. Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene. J. Neuropathol. Exp. Neurol., 2004, 63, 363-80.
166. Chinnery P. F. Neuroferritinopathy. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2005; 1993, Vol.
167. Jankovic, J.; Clarence-Smith, K. Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders. Expert Rev. Neurotherap., 2011, 11, 1509-23.
168. Hautot, D.; Pankhurst, Q. A.; Morris, C. M.; Curtis, A.; Burn, J.; Dobson, J. Preliminary observation of elevated levels of nanocrystalline iron oxide in the basal ganglia of neuroferritinopathy patients. Biochim. Biophys. Acta., 2007, 1772, 21-5.
169. Mancuso, M.; Davidzon, G.; Kurlan, R. M.; Tawil, R.; Bonilla, E.; Di, M. S.; Powers, J. M. Hereditary ferritinopathy: a novel mutation, its cellular pathology, and pathogenetic insights. J. Neuropathol. Exp. Neurol., 2005, 64, 280-94.
170. Deng, X.; Vidal, R.; Englander, E. W. Accumulation of oxidative DNA damage in brain mitochondria in mouse model of hereditary ferritinopathy. Neurosci. Lett., 2010, 479, 44-8.
171. Barbeito, A. G.; Garringer, H. J.; Baraibar, M. A.; Gao, X.; Arredondo, M.; Nunez, M. T.; Smith, M. A.; Ghetti, B.; Vidal, R. Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene. J. Neurochem., 2009, 109, 1067-78.
172. Cozzi, A.; Rovelli, E.; Frizzale, G.; Campanella, A.; Amendola, M.; Arosio, P.; Levi, S. Oxidative stress and cell death in cells expressing L-ferritin variants causing neuroferritinopathy. Neurobiol. Dis., 2010, 37, 77-85.
173. Barbeito, A. G.; Levade, T.; Delisle, M. B.; Ghetti, B.; Vidal, R. Abnormal iron metabolism in fibroblasts from a patient with the neurodegenerative disease hereditary ferritinopathy. Mol. Neurodegener., 2010, 5, 50.
174. Kruer, M., Gregory, A., Hogarth, P., and Hayflick, S. Static encephalopathy of childhood with neurodegeneration in adulthood (SENDA syndrome): a novel neurodegneration with brain iron accumulation (NBIA) phenotype. (oral correspondence). 2009.
175. Brueggemann, N.; Wuerfel, J. T.; Petersen, D.; Klein, C.; Hagenah, J.; Schneider, S. A. Idiopathic NBIA-clinical spectrum and transcranial sonography findings. Eur. J. Neurol., 2011, 18, e58-9.
176. Waldvogel, D.; van, G. P.; Hallett, M. Increased iron in the dentate nucleus of patients with Friedrich's ataxia. Ann. Neurol., 1999, 46, 123-5.
177. Levy, M.; Turtzo, C.; Llinas, R. H. Superficial siderosis: a case report and review of the literature. Nat. Clin. Pract. Neurol., 2007, 3, 54-8.
178. Catoire, H.; Dion, P.; Xiong, L.; Amari, M.; Gaudet, R.; Girard, S. L.; Noreau, A.; Gaspar, C.; Turecki, G.; Montplaisir, J. Y.; Parker, J. A.; Rouleau, G. A. Restless legs syndrome-associated MEIS1 risk variant influences iron homeostasis. Ann. Neurol., 2011, 70, 170-5.
179. Chang, M. H.; Hung, W. L.; Liao, Y. C.; Lee, Y. C.; Hsieh, P. F. Eye of the tiger-like MRI in parkinsonian variant of multiple system atrophy. J. Neural. Transm., 2009, 116, 861-6.
180. Davie, C. A.; Barker, G. J.; Machado, C.; Miller, D. H.; Lees, A. J. Proton magnetic resonance spectroscopy in Steele-Richardson-Olszewski syndrome. Mov. Disord., 1997, 12, 767-71.
181. Molinuevo, J. L.; Munoz, E.; Valldeoriola, F.; Tolosa, E. The eye of the tiger sign in cortical-basal ganglionic degeneration. Mov. Disord., 1999, 14, 169-71.
182. Santillo, A. F.; Skoglund, L.; Lindau, M.; Eeg-Olofsson, K. E.; Tovi, M.; Engler, H.; Brundin, R. M.; Ingvast, S.; Lannfelt, L.; Glaser, A.; Kilander, L. Frontotemporal dementia-amyotrophic lateral sclerosis complex is simulated by neurodegeneration with brain iron accumulation. Alzheimer Dis. Assoc. Disord., 2009, 23, 298-300.
183. Li, X.; Jankovic, J. Iron chelation and neuroprotection in neurodegenerative diseases. J. Neural. Transm., 2011, 118, 473-7.
184. Zhu, W.; Li, X.; Luo, F.; Kaur, D.; Andersen, J. K.; Jankovic, J.; Le, W. Genetic iron chelation protects against proteasome inhibition-induced dopamine neuron degeneration. Neurobiol. Dis., 2010, 37, 307-13.
185. Kwiatkowski, A.; Ryckewaert, G.; Jissendi, T. P.; Moreau, C.; Vuillaume, I.; Chinnery, P. F.; Destee, A.; Defebvre, L.; Devos, D. Long-term improvement under deferiprone in a case of neurodegeneration with brain iron accumulation. Parkinsonism Relat. Disord., 2012, 18, 110-2.
186. Abbruzzese, G.; Cossu, G.; Balocco, M.; Marchese, R.; Murgia, D.; Melis, M.; Galanello, R.; Barella, S.; Matta, G.; Ruffinengo, U.; Bonuccelli, U.; Forni, G. L. A pilot trial of deferiprone for neurodegeneration with brain iron accumulation. Haematologica, 2011, 96, 1708-11.
187. Forni, G. L.; Balocco, M.; Cremonesi, L.; Abbruzzese, G.; Parodi, R. C.; Marchese, R. Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation. Mov. Disord., 2008, 23, 904-7.
188. Zorzi, G.; Zibordi, F.; Chiapparini, L.; Bertini, E.; Russo, L.; Piga, A.; Longo, F.; Garavaglia, B.; Aquino, D.; Savoiardo, M.; Solari, A.; Nardocci, N. Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: Results of a phase II pilot trial. Mov. Disord., 2011, 26, 1756-9.
189. Ogretmen, B.; Hannun, Y. A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat. Rev., 2008, 4, 616.
190. Birbes, H.; El Bawabb; S.; Obeida, L. M.; Hannun, Y. A. Mitochondria and ceramide:intertwined roles in regulation of apoptosis. Adv. Enzyme Regul., 2002, 42, 113-29.
191. Skidmore, F. M.; Drago, V.; Foster, P.; Schmalfuss, I.; Heilman, K. M.; Streiff, R. Aceruloplasminemia with progressive atrophy without brain iron overload: treatment with oral chelation. J. Neurol. Neurosurg. Psychiatry, 2007.
192. Madsen, E.; Gitlin, J. D. Copper and iron disorders of the brain. Annu. Rev. Neurosci., 2007, 30, 317-37.
193. Vercueil, L.; Pollak, P.; Fraix, V.; Caputo, E.; Moro, E.; Benazzouz, A.; Xie, J.; Koudsie, A.; Benabid, A. L. Deep brain stimulation in the treatment of severe dystonia. J. Neurol., 2001, 248, 695-700.
194. Umemura, A.; Jaggi, J. L.; Dolinskas, C. A.; Stern, M. B.; Baltuch, G. H. Pallidal deep brain stimulation for longstanding severe generalized dystonia in Hallervorden-Spatz syndrome. Case report. J. Neurosurg., 2004, 100, 706-9.
195. Detante, O.; Vercueil, L.; Krack, P.; Chabardes, S.; Benabid, A. L.; Pollak, P. Off-period dystonia in Parkinson's disease but not generalized dystonia is improved by high-frequency stimulation of the subthalamic nucleus. Adv. Neurol., 2004, 94, 309-14.
196. Sharma, M. C.; Aggarwal, N.; Bihari, M.; Goyal, V.; Gaikwed, S.; Vaishya, S.; Sarkar, C. Hallervorden spatz disease: MR and pathological findings of a rare case. Neurol. India, 2005, 53, 102-4.
197. Shields, D. C.; Sharma, N.; Gale, J. T.; Eskandar, E. N. Pallidal stimulation for dystonia in pantothenate kinase-associated neurodegeneration. Pediatr. Neurol., 2007, 37, 442-5.
198. Isaac, C.; Wright, I.; Bhattacharyya, D.; Baxter, P.; Rowe, J. Pallidal stimulation for pantothenate kinase-associated neurodegeneration dystonia. Arch. Dis. Child, 2008, 93, 239-40.
199. Ge, M.; Zhang, K.; Ma, Y.; Meng, F. G.; Hu, W. H.; Yang, A. C.; Zhang, J. G. Bilateral subthalamic nucleus stimulation in the treatment of neurodegeneration with brain iron accumulation type 1. Stereotact. Funct. Neurosurg., 2011, 89, 162-6.
200. Neufeld, E. J. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood, 2006, 107, 3436-41.
201. Kell, D. G. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med. Genom., 2009, 2, 2-79.
202. Dusek, P.; Schneider S.A. Neurodegeneration with brain iron accumulation. Curr. Opin. Neurol., 2012, 25, 499-506.
203. King, M. W. www.themedicalbiochemistrypage.org/sphingolipids retrieved June 2011. Electronic Citation