Hallervorden-Spatz disease


Department of Neurology, Shahid Sadooghi Hospital, Isfahan, Iran


Hallervorden-Spatz disease (HSD) is a rare disorder characterized by progressive extrapyramidal dysfunction and dementia. Hallervorden and Spatz first described the disease, in 1922 as a form of familial brain degeneration characterized by iron deposition in the brain. Here we present four HSD cases with different clinical pictures.


1. Neumann M, Adler S, Schlüter O, Kremmer E, Benecke R, Kretzschmar HA. 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.  Back to cited text no. 1
2. Schneider SA, Hardy J, Bhatia KP. Iron accumulation in syndromes of neurodegeneration with brain iron accumulation 1 and 2: Causative or consequential? J Neurol Neurosurg Psychiatry 2009;80:589-90.  Back to cited text no. 2
3. Jankovic J, Kirkpatrick JB, Blomquist KA, Langlais PJ, Bird ED. Late-onset Hallervorden-Spatz disease presenting as familial parkinsonism. Neurology 1985;35:227-34.  Back to cited text no. 3
4. Grimes DA, Lang AE, Bergeron C. Late adult onset chorea with typical pathology of Hallervorden-Spatz syndrome. J Neurol Neurosurg Psychiatry 2000;69:392-5.  Back to cited text no. 4
5. Cooper GE, Rizzo M, Jones RD. Adult-onset Hallervorden-Spatz syndrome presenting as cortical dementia. Alzheimer Dis Assoc Disord 2000;14:120-6.  Back to cited text no. 5
6. Saito Y, Kawai M, Inoue K, Sasaki R, Arai H, Nanba E, et al. Widespread expression of alpha-synuclein and tau immunoreactivity in Hallervorden-Spatz syndrome with protracted clinical course. J Neurol Sci 2000;177:48-59.  Back to cited text no. 6
7. Hickman SJ, Ward NS, Surtees RA, Stevens JM, Farmer SF. How broad is the phenotype of Hallervorden-Spatz disease? Acta Neurol Scand 2001;103:201-3.  Back to cited text no. 7
8. Taylor TD, Litt M, Kramer P, Pandolfo M, Angelini L, Nardocci N, et al. Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. Nat Genet 1996;14:479-81.  Back to cited text no. 8
9. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 2001;28:345-9.  Back to cited text no. 9
10. Perry TL, Norman MG, Yong VW, Whiting S, Crichton JU, Hansen S, et al. Hallervorden-Spatz disease: Cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus. Ann Neurol 1985;18:482-9.  Back to cited text no. 10
11. Hayflick SJ. First scientific workshop on Hallervorden-Spatz syndrome: Executive summary. Pediatr Neurol 2001;25:99-101.  Back to cited text no. 11
12. Gregory A, Polster BJ, Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet 2009;46:73-80.  Back to cited text no. 12
13. Johnson MA, Kuo YM, Westaway SK, Parker SM, Ching KH, Gitschier J, et al. Mitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. Ann N Y Acad Sci 2004;1012:282-98.  Back to cited text no. 13
14. Kotzbauer PT, Truax AC, Trojanowski JQ, Lee VM. 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.  Back to cited text no. 14
15. Leoni V, Strittmatter L, Zorzi G, Zibordi F, Dusi S, Garavaglia B, et al. Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations. Mol Genet Metab 2012;105:463-71.  Back to cited text no. 15
16. Swaiman KF. Hallervorden-Spatz syndrome and brain iron metabolism. Arch Neurol 1991;48:1285-93.  Back to cited text no. 16
17. Halliday W. The nosology of Hallervorden-spatz disease. J Neurol Sci 1995;134 Suppl:84-91.  Back to cited text no. 17
18. Vakili S, Drew AL, Von Schuching S, Becker D, Zeman W. Hallervorden-Spatz syndrome. Arch Neurol 1977;34:729-38.  Back to cited text no. 18
19. Zimmerman AW, Stover ML, Grasso JA. Uptake of 59Fe by skin fibroblasts and MAO activity in platelets from patients with Hallervorden-Spatz syndrome. Neurology 1981;51:48.  Back to cited text no. 19
20. Swaiman KF, Smith SA, Trock GL, Siddiqui AR. Sea-blue histiocytes, lymphocytic cytosomes, movement disorder and 59Fe-uptake in basal ganglia: Hallervorden-Spatz disease or ceroid storage disease with abnormal isotope scan? Neurology 1983;33:301-5.  Back to cited text no. 20
21. Alberca R, Rafel E, Chinchon I, Vadillo J, Navarro A. Late onset parkinsonian syndrome in Hallervorden-Spatz disease. J Neurol Neurosurg Psychiatry 1987;50:1665-8.  Back to cited text no. 21
22. Hermann W, Reuter M, Barthel H, Dietrich J, Georgi P, Wagner A. Diagnosis of Hallervorden-Spatz disease using MRI, (123)I-beta-CIT-SPECT and (123)I-IBZM-SPECT. Eur Neurol 2000;43:187-8.  Back to cited text no. 22
23. Feliciani M, Curatolo P. Early clinical and imaging (high-field MRI) diagnosis of Hallervorden-Spatz disease. Neuroradiology 1994;36:247-8.  Back to cited text no. 23
24. Shah J, Patkar D, Patankar T, Krishnan A, Prasad S, Limdi J. Hallervorden Spatz disease: MR imaging. J Postgrad Med 1999;45:114-7.  Back to cited text no. 24
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25. McNeill A, Birchall D, Hayflick SJ, Gregory A, Schenk JF, Zimmerman EA, et al. T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology 2008;70:1614-9.  Back to cited text no. 25
26. Sethi KD, Adams RJ, Loring DW, el Gammal T. Hallervorden-Spatz syndrome: Clinical and magnetic resonance imaging correlations. Ann Neurol 1988;24:692-4.  Back to cited text no. 26
27. Delgado RF, Sanchez PR, Speckter H, Then EP, Jimenez R, Oviedo J, et al. 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.  Back to cited text no. 27
28. Chiapparini L, Savoiardo M, D'Arrigo S, Reale C, Zorzi G, Zibordi F, et al. The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration. Neuropediatrics 2011;42:159-62.  Back to cited text no. 28