Original Article
Genetic, Clinical, and Radiographic Delineation of Hallervorden–Spatz Syndrome
N Engl J Med 2003; 348:33-40January 2, 2003
- Abstract
Background
Hallervorden–Spatz syndrome is an autosomal recessive disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. Many patients with this disease have mutations in the gene encoding pantothenate kinase 2 (PANK2); these patients are said to have pantothenate kinase–associated neurodegeneration. In this study, we compared the clinical and radiographic features of patients with Hallervorden–Spatz syndrome with and without mutations in PANK2.
Methods
One hundred twenty-three patients from 98 families with a diagnosis of Hallervorden–Spatz syndrome were classified on the basis of clinical assessment as having classic disease (characterized by early onset with rapid progression) or atypical disease (later onset with slow progression). Their genomic DNA was sequenced for PANK2 mutations.
Results
All patients with classic Hallervorden–Spatz syndrome and one third of those with atypical disease had PANK2 mutations. Whereas almost all mutations in patients with atypical disease led to amino acid changes, those in patients with classic disease more often resulted in predicted protein truncation. Patients with atypical disease who had PANK2 mutations were more likely to have prominent speech-related and psychiatric symptoms than patients with classic disease or mutation-negative patients with atypical disease. In all patients with pantothenate kinase–associated neurodegeneration, whether classic or atypical, T2-weighted magnetic resonance imaging (MRI) of the brain showed a specific pattern of hyperintensity within the hypointense medial globus pallidus. This pattern was not seen in any patients without mutations.
Conclusions
PANK2 mutations are associated with all cases of classic Hallervorden–Spatz syndrome and one third of cases of atypical disease. A specific MRI pattern distinguishes patients with PANK2 mutations. Predicted levels of pantothenate kinase 2 protein correlate with the severity of disease.
Media in This Article
Figure 1
Patterns on T2-Weighted Brain Magnetic Resonance Imaging.Table 1
PANK2 Mutations Identified in Patients with Pantothenate Kinase–Associated Neurodegeneration.Article Activity
- Article
The diagnosis of Hallervorden–Spatz syndrome applies to a spectrum of disorders that share the common features of neurodegeneration and iron accumulation in the brain.1,2 Hallervorden–Spatz syndrome with early onset and rapid progression is the originally reported, classic form of the disease.3 It presents in childhood with dystonia, dysarthria, and rigidity and has a relentlessly progressive course, culminating in early death. Pigmentary degeneration of the retina may accompany this form of the disease, and iron deposition in the basal ganglia is evident on magnetic resonance imaging (MRI) and postmortem examination.1 In an atypical form of Hallervorden–Spatz syndrome, the onset of extrapyramidal defects is later and the progression of the disease is slower and more variable, with accumulation of iron in the basal ganglia. Atypical disease is clinically heterogeneous and is thought to encompass several disorders.1,4,5 In addition, the condition of some patients does not fit the diagnostic criteria for Hallervorden–Spatz syndrome, yet the atypical form of the disease remains the diagnosis that best fits their signs and symptoms.4,6,7
Recently we discovered that many cases of Hallervorden–Spatz syndrome result from mutations in a gene located on chromosome 20p13.8 The culprit gene (PANK2) encodes a novel pantothenate kinase, a key regulatory enzyme in the biosynthesis of coenzyme A.8 We speculated that a deficiency of this enzyme could lead to neurodegeneration and iron accumulation, and we proposed a new descriptive term for the resulting autosomal recessive error of metabolism: pantothenate kinase–associated neurodegeneration (Online Mendelian Inheritance in Man number 234200).
In the current study, we determined the genotype of patients with classic and atypical Hallervorden–Spatz syndrome and reviewed their medical records to assess whether there was a correlation between clinical manifestations or radiographic findings and the presence of PANK2 mutations.
Methods
Subjects
Subjects were recruited internationally by means of announcements posted in neurology and genetics journals, on a pediatric-neurology list server, and on the Web sites of the Hallervorden–Spatz Syndrome Association (http://www.hssa.org) and the National Organization for Rare Disorders (http://www.rarediseases.org). We identified 186 patients from 145 families who had extrapyramidal defects and radiographic evidence of iron deposition in the basal ganglia. We examined 28 of the subjects. For the remainder, samples were sent by referring physicians and clinical and laboratory data were obtained from records and MRI scans. Detailed clinical information and DNA samples were collected from the patients after they had given written informed consent. The protocol was approved by the institutional review boards of the Oregon Health and Science University or the University of California, San Francisco. We gathered all possible clinical information, including the age at onset of disease and presenting symptoms; results of neurologic and ophthalmologic examinations; results of electrical studies, including electroencephalography, electromyography, electroretinography, and visual evoked potentials; and brain MRI scans. Clinical information was insufficient for 63 of the 186 patients, and our analysis is therefore based on the remaining 123 patients from 98 families.
Patients were classified as having either classic disease (66 patients) or atypical disease (57 patients). Early-onset, rapidly progressive (classic) disease was usually evident by the age of 10 years and was manifested by dystonia, progression to severe disability by 20 years of age, and radiographic changes indicating a high iron content in the basal ganglia. Those with atypical disease included all other patients with extrapyramidal dysfunction and radiographic evidence of iron accumulation in the basal ganglia. The atypical disease usually also had a later onset and a more slowly progressive course.
Analysis of Mutations
Primers were designed to amplify each of the seven exons of PANK2. Polymerase-chain-reaction–amplified DNA was sequenced in both the forward and the reverse directions and compared with control DNA. Mutations were classified as null if they were predicted to result in premature protein termination (including frame shifts, nonsense mutations, and mutations altering splice-donor and acceptor sequences); missense mutations were defined as those causing the substitution of one amino acid for another.
Statistical Analysis
Chi-square analyses were conducted with the use of an online tool (http://www.georgetown.edu/cball/webtools/web_chi.html).
Results
Genetic Findings
PANK2 mutations were found in 66 of the 98 families of patients with Hallervorden–Spatz syndrome (Table 1Table 1
PANK2 Mutations Identified in Patients with Pantothenate Kinase–Associated Neurodegeneration.). Of 49 families whose members had classic disease, all had mutations in PANK2. Of 49 families whose members had atypical disease, mutations were found in 17 (35 percent). Null mutations were found in 36 of 92 alleles in patients with classic disease, but in only 2 of 31 alleles in patients with atypical disease. All patients with two null alleles had the classic form of the disease.Two PANK2 mutations, both of them missense mutations, accounted for one third of the disease alleles. G411R constituted 31 disease-related alleles in 27 families, and T418M occurred 10 times in 6 families. G411R was seen on a background of a shared haplotype derived from markers that spanned 1 cM and flanked PANK2, indicating a founder effect for this mutation (data not shown). The majority (81 percent) of the 27 families with the G411R mutation were of European descent. Neither of these sequence changes was seen in any of more than 100 control chromosomes.
An intriguing feature of the G411R mutation is that in six families harboring this mutation (four with classic disease and two with atypical disease), no mutation was detected on the other chromosome. Families with only one identified mutation were not distinguishable from those with two. With our current strategy, some mutations would be undetectable (e.g., promoter mutations). However, of nine families with single mutant alleles, six had an allele with a G411R mutation. This observation is striking because mutations in both alleles were detected in nearly all families, and it suggests that G411R might be semidominant, with one allele sufficient to cause disease given certain genetic backgrounds. Contrary to this hypothesis, no disease phenotype was observed in G411R-heterozygous carrier parents of affected persons. Environmental exposure or modifier effects of other genes, including those for enzymes downstream in the coenzyme A synthetic pathway, might also have a role in the pathogenesis of the disease, in concert with the G411R allele.
Clinical Findings
On the basis of the existing clinical information, the 123 patients who were studied were not different from the 63 who were excluded because of insufficient clinical information. Information about each clinical characteristic was not available for every patient included in our study cohort.
The clinical features of our cohort of 66 PANK2-mutation–positive patients with classic disease were remarkably homogeneous. Pantothenate kinase–associated neurodegeneration usually presented before the age of 6 years (in 88 percent of cases), with a mean (±SD) age at onset of 3.4±3.0 years (range, 0.5 to 12). The most common presenting symptoms were gait or postural difficulties, which occurred in 40 of 51 patients for whom information was available (78 percent). These symptoms were much less common among patients who had the later-onset form of the disease or who did not have PANK2 mutations (P<0.001).
The predominant neurologic features were extrapyramidal and included dystonia, dysarthria, rigidity, and choreoathetosis (51 of 52 patients [98 percent]). Dystonia was a nearly constant early manifestation (45 of 52 patients [87 percent]). Early dystonia often involved the cranial and limb musculature, with axial dystonia predominating later. Involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor toe signs, was common (13 of 52 patients [25 percent]), as was cognitive decline (15 of 52 patients [29 percent]). Seizures were not reported in any patient with classic disease. Forty-five of 66 patients with classic disease (68 percent) had clinical or electroretinographic evidence of retinopathy. Optic atrophy was infrequent, occurring in only 2 of 66 patients (3 percent). Acanthocytosis was reported in 8 percent of patients with classic disease. Since acanthocytosis is not sought routinely, its true prevalence among patients with pantothenate kinase–associated neurodegeneration remains uncertain. We observed that classic pantothenate kinase–associated neurodegeneration progressed at a nonuniform rate, with periods of marked deterioration, often lasting one to two months, interspersed with longer periods of clinical stability. The majority of patients with classic pantothenate kinase–associated neurodegeneration (85 percent) became nonambulatory within 15 years after the onset of the disease.
The clinical features of the 23 patients with atypical Hallervorden–Spatz syndrome and PANK2 mutations were heterogeneous. These patients were significantly older at the onset of the disease than patients with classic disease (13.7±5.9 years [range, 1 to 28] vs. 3.4±3.0 years [range, 0.5 to 12], P<0.001). In rare cases, these patients had very early nonspecific problems (3 of 20 patients for whom information was available [15 percent]), including developmental delay (2 of 20 patients [10 percent]). Extrapyramidal defects developed in 16 of 22 patients with atypical disease (73 percent), but dystonia and rigidity were generally less severe and more slowly progressive than in patients with classic disease. Most of these patients (14 of 22 [64 percent]) continued to be able to walk into adulthood, but in many the disease eventually progressed to loss of independent ambulation. Spasticity, hyperreflexia, and other signs of corticospinal tract involvement were common (3 of 17 patients [18 percent]) and progressive, eventually limiting ambulation. Freezing was reported in 3 of 20 patients with atypical disease (15 percent). Clinical evidence of retinopathy or optic atrophy was much less common than in patients with classic disease (3 of 15 patients [20 percent], P<0.001).
An unexpected finding was that in 9 of the 23 patients with atypical pantothenate kinase–associated neurodegeneration (39 percent), difficulty with speech, including palilalia (repetition of words or phrases) and dysarthria, was either the sole presenting feature or part of the early disease. In contrast, no patient with classic pantothenate kinase–associated neurodegeneration presented with a speech defect (although dysarthria developed later in 16 of these patients). Psychiatric symptoms with cognitive decline, reminiscent of frontotemporal dementia, were prominent in patients with atypical pantothenate kinase–associated neurodegeneration (6 of 18 patients for whom information was available [33 percent]) and rare in patients with classic pantothenate kinase–associated neurodegeneration; these symptoms included personality changes with impulsivity and violent outbursts, depression, and emotional lability.
Additionally compelling is the clinical comparison between patients with a diagnosis of atypical Hallervorden–Spatz syndrome who had a PANK2 mutation and those who did not. Among the patients for whom the presenting symptoms were noted in the medical records, 6 of 18 with atypical disease and PANK2 mutations presented with speech difficulties, whereas none of the 17 with atypical disease who had no PANK2 mutations had this presentation (P<0.05). Psychiatric symptoms developed in 6 of 18 patients with atypical disease and PANK2 mutations but in no patients with atypical disease without PANK2 mutations (P<0.05). Otherwise, patients without PANK2 mutations were similar to those with mutations: they generally had extrapyramidal and corticospinal tract dysfunction; their mean age at onset of the disease was 7.0±9.9 years (range, 0.5 to 38); and their family histories indicated that they had affected siblings or that their cases were sporadic, both findings that are consistent with autosomal recessive inheritance.
Radiographic Findings
A striking correlation was found between the MRI findings and the presence or absence of PANK2 mutations in patients with Hallervorden–Spatz syndrome. All MRI scans reviewed from 28 patients with PANK2 mutations (24 with classic disease and 4 with atypical disease) showed bilateral areas of hyperintensity within a region of hypointensity in the medial globus pallidus on T2-weighted images, a pattern known as “eye of the tiger”9 (Figure 1Figure 1
Patterns on T2-Weighted Brain Magnetic Resonance Imaging.). Moreover, reports of MRI scans from 41 additional mutation-positive patients (36 with classic and 5 with atypical disease) described them in detail as showing these specific changes. Indeed, no PANK2-mutation–positive patients lacking the eye-of-the-tiger sign have been found.We also found the reciprocal to be true; that is, we found no evidence of the eye-of-the-tiger pattern on MRI in any mutation-negative patient. MRI films from 16 mutation-negative patients showed only hypointensity in the globus pallidus on T2-weighted images (Figure 1). In this group of patients, cerebellar atrophy and iron deposition in the red nucleus and dentate nucleus were common features that were not seen in patients who had classic disease or in those who had atypical disease with PANK2 mutations. Thus, the eye-of-the-tiger sign is strongly correlated with PANK2 mutations (P<0.001).
On the basis of this correlation, we assessed the value of the brain MRI alone in predicting mutation status. In a small subgroup of symptomatic patients with Hallervorden–Spatz syndrome who were not included in our study because of insufficient clinical information, we identified six patients solely by the presence of the eye-of-the-tiger sign and analyzed their DNA for PANK2 mutations. All six patients were found to have PANK2 mutations on both chromosomes, a result further supporting the correlation between the presence of these mutations and the eye-of-the-tiger sign.
Discussion
We identified mutations in the PANK2 gene in a large subgroup of patients with Hallervorden–Spatz syndrome. All patients with classic disease had PANK2 mutations, suggesting that patients with early-onset, rapidly progressive disease will consistently prove to have inherited defects in pantothenate kinase 2. Among patients with atypical disease, those with PANK2 mutations were much more likely to have speech and psychiatric problems than were mutation-negative patients. Most compelling is our finding of a one-to-one correlation between the MRI eye-of-the-tiger pattern and the presence of a PANK2 mutation, regardless of the severity of the disease. In Table 2Table 2
Phenotypic Features of Pantothenate Kinase–Associated Neurodegeneration., we propose clinical descriptions of the major forms of pantothenate kinase–associated neurodegeneration.Our data have implications for the differential diagnosis of Hallervorden–Spatz syndrome and for treatment of pantothenate kinase–associated neurodegeneration. Patients with the classic form of Hallervorden–Spatz syndrome should provisionally be given the diagnosis of pantothenate kinase–associated neurodegeneration, awaiting confirmation by DNA analysis. Patients with atypical Hallervorden–Spatz syndrome who present with speech and psychiatric disorders and whose brain MRI scans have the eye-of-the-tiger sign should undergo analysis for PANK2 mutations. The fact that almost all patients with atypical disease and pantothenate kinase–associated neurodegeneration have missense mutations indicates that many of them may have residual pantothenate kinase 2 activity. We speculate that supplemental pantothenate (vitamin B5) could compensate for the partial enzymatic deficiency in these patients, possibly ameliorating or retarding the symptoms. Such treatment might even prove effective in patients with classic disease who have partial enzyme activity. However, these hypotheses require evaluation.
Two clinical observations warrant further discussion. First, although the profile of classic pantothenate kinase–associated neurodegeneration is consistent with that presented in the many reports of patients with early-onset Hallervorden–Spatz syndrome,1,3,10-12 pigmentary degeneration of the retina was much more common in our patients than has been reported in others.1,13 Retinopathy develops early, though it may be recognized only when a full diagnostic evaluation is performed. As a corollary, we found it uncommon for retinopathy to develop later in patients with normal results on funduscopic examination at the time of diagnosis.
Second, we have delineated the dominant neurologic features of patients with atypical pantothenate kinase–associated neurodegeneration, which differ from those seen in the classic form of the disease. These features, which include severe palilalia, dysarthria, dystonia (which may be intermittent and fluctuating), perseverative behavior and movements, and freezing, have not been widely recognized in this disease.14-16 Freezing during ambulation, especially when turning corners or encountering surface variations, is strikingly similar to changes seen in Parkinson's disease.15 Psychiatric symptoms, including depression and psychosis, were common in the patients with atypical disease in our study. In several patients with atypical disease whose first major symptom was palilalia, psychiatric abnormalities were misinterpreted as the cause of the speech defect. Progressive dementia occurs in atypical pantothenate kinase–associated neurodegeneration.
The one-to-one correlation between a specific radiographic finding, the eye-of-the-tiger sign, and mutations in a single gene, PANK2, is extraordinary. Clearly, the medial globus pallidus is especially sensitive to deficiency of pantothenate kinase 2, one of four pantothenate kinases encoded by the human genome. The eye-of-the-tiger pattern may reflect tissue necrosis and edema (seen on T2-weighted MRI as hyperintensity) within a region of iron deposition (seen as hypointensity), but how a deficiency in pantothenate kinase 2 leads to these changes remains speculative. Previously, we suggested that accumulated cysteine, which would normally condense with phosphopantothenate, and cysteine-containing compounds may form complexes with iron and exacerbate oxidative damage in this brain structure.8
Pantothenate kinase–associated neurodegeneration is one of three extrapyramidal disorders associated with increased amounts of brain iron for which the molecular basis has been defined. The other two disorders, neuroferritinopathy, which results from mutations in the ferritin light-chain gene,17 and aceruloplasminemia, which results from mutations in the gene encoding ceruloplasmin,18 are of adult onset and can be distinguished from pantothenate kinase–associated neurodegeneration on the basis of the clinical presentation, MRI findings, and results of genetic testing.
Additional biochemical markers of pantothenate kinase–associated neurodegeneration may help us understand its pathologic effects and develop therapeutic targets. Acanthocytosis and a defect in plasma lipoproteins have been associated with mutations in PANK2.19 These systemic features will help focus future biochemical investigations. With better understanding of the metabolic perturbations in pantothenate kinase–associated neurodegeneration, we may be able to devise neuroprotective interventions to prevent exacerbations and thereby slow the progression of the disease.
Currently, however, we are left with no imaging or DNA-based tool for the definitive diagnosis of the disease in two thirds of patients with atypical Hallervorden–Spatz syndrome. Conceivably, pantothenate and coenzyme A metabolism may be perturbed in these patients or in patients with other neurodegenerative disorders. For example, patients with normal amounts of brain iron who have early-onset parkinsonism, severe speech impairment, perseverative movements, or pigmentary retinopathy may have alterations in these metabolic pathways. Indeed, the spectrum of diseases that are associated with inborn errors of pantothenate or coenzyme A metabolism is likely to expand.
The eponymous term “Hallervorden–Spatz syndrome” has fallen into disfavor in view of the unethical activities of the German neuropathologists Hallervorden and Spatz during World War II.20 We encourage the use of the term “pantothenate kinase–associated neurodegeneration” for the majority of patients with Hallervorden–Spatz syndrome who have proved or suspected mutations in PANK2. For the remainder, we propose the term “neurodegeneration with brain iron accumulation.”
Supported by grants from the National Eye Institute and the Sandler Neurogenetics Center at the University of California, San Francisco. Dr. Gitschier is an investigator of the Howard Hughes Medical Institute.
We are indebted to the patients and their families; to our clinical collaborators Drs. J. Jankovic, M. Thomas, J. Guimarães, J. Molinuevo, F. Martí, M.A.M. Salih, J. Coppeto, J.P. Harpey, M. Shevell, M. Piñeda, G. Kurlemann, S. Davis, H. Hattori, K. Sethi, M. Pandolfo, L. Angelini, N. Nardocci, A. Malandrini, J. Penzien, G. Mortier, M. Hoeltzenbein, J.A. Urtizberea, D. Buckley, C. Haenggeli, A. Bottani, B. Beinlich, J. Østergaard, S. Bundey, F. Stögbauer, K. Nørgaard Hansen, C. Yalcinkaya, A. Feigenbaum, Z. Liptai, J. Carlo, P. Blasco, A. Zimmerman, R. Cilio, E. Bertini, G. Worley, U. Thyen, M. Melis, G. Cossu, J. Menkes, K. Hollódy, A. Barrett, S. Simpson, C. Schrander-Stumpel, H. Chaabouni, R. Gatti, H. Topaloglu, M. Nigro, F. Hisama, N.R.M. Buist, B. Ben-Zeév, A. Macaya, B. Korf, P. Heydemann, S. Abbs, R. Robinson, L. Shinobu, E. Dooling, P. Wheeler, P. Rosman, W. Wasiewski, P. Castelnau, P. Evrard, R. Haslam, M. Filocamo, M. Karwacki, T. Kmieæ, S. Frucht, T. Konishi, M. Regina Reyes, M. Al-Mateen, K. Weidenheim, M. Delgado, S. Johnsen, S. Golembowski, W. Ondo, S. Bohlega, R. Bustamante, O. Fernandez, M. Wiznitzer, H. Morgan, I. Butler, T. Babb, D. Sanderson, M. Williams, C. Harding, R. Steiner, S. Toor, E. Thompson, J. MacKenzie, J. Clyman, J.J. Higgins, and D. Fornoff; to P. Hogarth and J. Nutt for critical review of the manuscript; to the Oregon Health and Science University Molecular Microbiology and Immunology Sequencing Core; and to the Hallervorden–Spatz Syndrome Association.
Source Information
From the Departments of Molecular and Medical Genetics, Pediatrics, and Neurology, School of Medicine, Oregon Health and Science University, Portland (S.J.H., S.K.W., M.A.J., K.H.L.C.); and the Howard Hughes Medical Institute and the Departments of Medicine and Pediatrics, University of California, San Francisco (B.L., B.Z., J.G.).
Address reprint requests to Dr. Hayflick at the Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Mailcode L-103a, Portland, OR 97201-3098, or at hayflick@ohsu.edu.
- References
References
1
Dooling EC ,Schoene WC ,Richardson EP Jr . Hallervorden-Spatz syndrome. Arch Neurol 1974;30:70-83
Web of Science | Medline2
Swaiman KF . Hallervorden-Spatz syndrome and brain iron metabolism. Arch Neurol 1991;48:1285-1293
Web of Science | Medline3
Hallervorden J ,Spatz H . Eigenartige Erkrankung im extrapyramidalen System mit besonderer Beteiligung des Globus pallidus und der Substantia nigra. Z Gesamte Neurol Psychiatr 1922;79:254-302
CrossRef4
Halliday W . The nosology of Hallervorden-Spatz disease. J Neurol Sci 1995;134:Suppl:84-91
CrossRef | Web of Science | Medline5
Hickman SJ ,Ward NS ,Surtees RA ,Stevens JM ,Farmer SF . How broad is the phenotype of Hallervorden-Spatz disease? Acta Neurol Scand 2001;103:201-203
CrossRef | Web of Science | Medline6
Jankovic J ,Kirkpatrick JB ,Blomquist KA ,Langlais PJ ,Bird ED . Late-onset Hallervorden-Spatz disease presenting as familial parkinsonism. Neurology 1985;35:227-234
Web of Science | Medline7
Coppeto JR ,Lessell S . A familial syndrome of dystonia, blepharospasm, and pigmentary retinopathy. Neurology 1990;40:1359-1363
Web of Science | Medline8
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;28:345-349
CrossRef | Web of Science | Medline9
Sethi KD ,Adams RJ ,Loring DW ,el Gammal T . Hallervorden-Spatz syndrome: clinical and magnetic resonance imaging correlations. Ann Neurol 1988;24:692-694
CrossRef | Web of Science | Medline10
Hallervorden J . Über eine familiäre Erkrankung im extrapyramidalen System. Dtsch Z Nervenheilkd 1924;81:204-210
CrossRef11
Roth AM ,Hepler RS ,Mukoyama M ,Cancilla PA ,Foos RY . Pigmentary retinal dystrophy in Hallervorden-Spatz disease: clinicopathological report of a case. Surv Ophthalmol 1971;16:24-3512
Swisher CN ,Menkes JH ,Cancilla PA ,Dodge PR . Coexistence of Hallervorden-Spatz disease with acanthocytosis. Trans Am Neurol Assoc 1972;97:212-21613
Luckenbach MW ,Green WR ,Miller NR ,Moser HW ,Clark AW ,Tennekoon G . Ocular clinicopathologic correlation of Hallervorden-Spatz syndrome with acanthocytosis and pigmentary retinopathy. Am J Ophthalmol 1983;95:369-382
Web of Science | Medline14
Nardocci N ,Rumi V ,Combi ML ,Angelini L ,Mirabile D ,Bruzzone MG . Complex tics, stereotypies, and compulsive behavior as clinical presentation of a juvenile progressive dystonia suggestive of Hallervorden-Spatz disease. Mov Disord 1994;9:369-371
CrossRef | Web of Science | Medline15
Guimaraes J ,Santos JV . Generalized freezing in Hallervorden-Spatz syndrome: case report. Eur J Neurol 1999;6:509-513
CrossRef | Web of Science | Medline16
Morphy MA ,Feldman JA ,Kilburn G . Hallervorden-Spatz disease in a psychiatric setting. J Clin Psychiatry 1989;50:66-68
Web of Science | Medline17
Curtis AR ,Fey C ,Morris CM , et al. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet 2001;28:350-354
CrossRef | Web of Science | Medline18
Gitlin JD . Aceruloplasminemia. Pediatr Res 1998;44:271-276
CrossRef | Web of Science | Medline19
Ching KHL ,Westaway SK ,Levinson B , et al. HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. Neurology 2002;58:1673-1674
Web of Science | Medline20
Shevell M . Racial hygiene, active euthanasia, and Julius Hallervorden. Neurology 1992;42:2214-2219
Web of Science | Medline
- Citing Articles (135)
Citing Articles
1
Mario Mascalchi, Alessandra Vella, Roberto Ceravolo. (2012) Movement disorders: role of imaging in diagnosis. Journal of Magnetic Resonance Imaging 35:2, 239-256
CrossRef2
Fleming, Robert E., Ponka, Prem, . (2012) Iron Overload in Human Disease. New England Journal of Medicine 366:4, 348-359
Full Text3
Michael J. Keogh, Patricia Jonas, Alan Coulthard, Patrick F. Chinnery, John Burn. (2012) Neuroferritinopathy: a new inborn error of iron metabolism. neurogenetics
CrossRef4
R. Fermin-Delgado, P. Roa-Sanchez, H. Speckter, E. Perez-Then, D. Rivera-Mejia, B. Foerster, P. Stoeter. (2012) Involvement of Globus Pallidus and Midbrain Nuclei in Pantothenate Kinase-Associated Neurodegeneration. Clinical Neuroradiology
CrossRef5
Emiko Ohta, Yoshihisa Takiyama. (2012) MRI Findings in Neuroferritinopathy. Neurology Research International 2012, 1-7
CrossRef6
Petr Dusek, Joseph Jankovic, Weidong Le. (2012) Iron dysregulation in movement disorders. Neurobiology of Disease
CrossRef7
Szu-Kuan Yang, Chaur-Jongh Hu, Rey-Yue Yuan, Hung-Jung Wang, Jau-Jiuan Sheu. (2011) Presence of the Eye-of-the-tiger Sign on Magnetic Resonance Imaging in a Subject of Atypical Hallervorden-Spatz Syndrome Lacking Pantothenate Kinase 2 Mutation. Journal of Experimental & Clinical Medicine
CrossRef8
Vladimir S. Kostić, Marina Svetel, Milija Mijajlović, Aleksandra Pavlović, Milica Ječmenica-Lukić, Dušan Kozić. (2011) Transcranial sonography in pantothenate kinase-associated neurodegeneration. Journal of Neurology
CrossRef9
K. A. M. Pauls, L. Timmermann. (2011) Deep Brain Stimulation in Pantothenate Kinase Associated Neurodegeneration: challenges for the future. European Journal of Neurologyno-no
CrossRef10
B. C. Lim, C.-S. Ki, A. Cho, H. Hwang, K. J. Kim, Y. S. Hwang, Y. E. Kim, J. Y. Yun, B. S. Jeon, Y. H. Lim, S. H. Paek, J. H. Chae. (2011) Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation. European Journal of Neurologyno-no
CrossRef11
Daniela Rossi, Elisa De Grandis, Chiara Barzaghi, Monica Mascaretti, Barbara Garavaglia, Elisabetta Zanotto, Giovanni Morana, Roberta Biancheri. (2011) Early-onset neurodegeneration with brain iron accumulation due to PANK2 mutation. Brain and Development
CrossRef12
Takashi Haraguchi, Seishi Terada, Hideki Ishizu, Osamu Yokota, Hidenori Yoshida, Naoya Takeda, Yuki Kishimoto, Naoko Katayama, Hiroshi Takata, Motohiro Akagi, Shigetoshi Kuroda, Yuetsu Ihara, Yosuke Uchitomi. (2011) Coexistence of TDP-43 and tau pathology in neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome). Neuropathology 31:5, 531-539
CrossRef13
John E. Duda, Kurt A. Jellinger. 2011. Neurodegeneration with Brain Iron Accumulation. , 446-455.
CrossRef14
Chaw-Liang Chang, Chih-Ming Lin. (2011) Eye-of-the-Tiger sign is not Pathognomonic of Pantothenate Kinase-Associated Neurodegeneration in Adult Cases. Brain and Behavior 1:1, 55-56
CrossRef15
Jan Liman, Andreas Wellmer, Kevin Rostasy, Mathias Bähr, Pawel Kermer. (2011) Transcranial ultrasound in neurodegeneration with brain iron accumulation (NBIA). European Journal of Paediatric Neurology
CrossRef16
Roberto Erro, Marianna Amboni, Carmine Vitale, Katia Longo, Mariangela Rocco, Carmela Russo, Sabina Pappatà, Arturo Brunetti, Paolo Barone. (2011) The “eye of the tiger” sign in pure akinesia with gait freezing. Neurological Sciences 32:4, 703-705
CrossRef17
Giovanna Zorzi, Federica Zibordi, Luisa Chiapparini, Enrico Bertini, Lidia Russo, Antonio Piga, Filomena Longo, Barbara Garavaglia, Domenico Aquino, Mario Savoiardo, Alessandra Solari, Nardo Nardocci. (2011) Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: Results of a phase II pilot trial. Movement Disorders 26:9, 1755-1759
CrossRef18
Andrés Berardo, Ana Yanina Dahi. (2011) Forma atípica de neurodegeneración asociada a pantotenato quinasa (PKAN) a raíz de un caso clínico en un neuropsiquiátrico. Neurología Argentina
CrossRef19
A. Moráis López, J. Dalmau Serra. (2011) Importancia de la ferropenia en el niño pequeño: repercusiones y prevención. Anales de Pediatría 74:6, 415.e1-415.e10
CrossRef20
Allison Gregory, Susan J. Hayflick. (2011) Genetics of Neurodegeneration with Brain Iron Accumulation. Current Neurology and Neuroscience Reports 11:3, 254-261
CrossRef21
MANJU A KURIAN, ALASDAIR MCNEILL, JEAN-PIERRE LIN, EAMONN R MAHER. (2011) Childhood disorders of neurodegeneration with brain iron accumulation (NBIA). Developmental Medicine & Child Neurology 53:5, 394-404
CrossRef22
Mark Walterfang, Andrew Evans, Jeffrey Chee Leong Looi, Hans H. Jung, Adrian Danek, Ruth H. Walker, Dennis Velakoulis. (2011) The neuropsychiatry of neuroacanthocytosis syndromes. Neuroscience & Biobehavioral Reviews 35:5, 1275-1283
CrossRef23
Chloe Miu Mak, Bun Sheng, Hencher Han-chih Lee, Kwok-kwong Lau, Wing-tak Chan, Ching-wan Lam, Yan-wo Chan. (2011) Young-Onset Parkinsonism in a Hong Kong Chinese Man With Adult-Onset Hallervorden–Spatz Syndrome. International Journal of Neuroscience 121:4, 224-227
CrossRef24
RACHEL MAHONEY, RICHARD SELWAY, JEAN-PIERRE LIN. (2011) Cognitive functioning in children with pantothenate-kinase-associated neurodegeneration undergoing deep brain stimulation. Developmental Medicine & Child Neurology 53:3, 275-279
CrossRef25
Stanley Fahn, Joseph Jankovic, Mark Hallett. 2011. Chorea, ballism, and athetosis. , 335-349.
CrossRef26
Ruth H. Walker, Vincent P. Schulz, Irina R. Tikhonova, Milind C. Mahajan, Shrikant Mane, Maritza Arroyo Muniz, Patrick G. Gallagher. (2011) Genetic diagnosis of neuroacanthocytosis disorders using exome sequencing. Movement Disordersn/a-n/a
CrossRef27
Michael E. Webb, Alison G. Smith. 2011. Pantothenate Biosynthesis in Higher Plants. , 203-255.
CrossRef28
Stanley Fahn, Joseph Jankovic, Mark Hallett. 2011. Atypical parkinsonism, parkinsonism-plus syndromes, and secondary parkinsonian disorders. , 197-240.
CrossRef29
Stanley Fahn, Joseph Jankovic, Mark Hallett. 2011. Dystonia. , 259-292.
CrossRef30
Alisdair Mcneill, Patrick F. Chinnery. 2011. Neurodegeneration with brain iron accumulation. , 161-172.
CrossRef31
Hans H Jung, Adrian Danek, Ruth H Walker. (2011) Neuroacanthocytosis Syndromes. Orphanet Journal of Rare Diseases 6:1, 68
CrossRef32
Stanley Fahn, Joseph Jankovic, Mark Hallett. 2011. Clinical overview and phenomenology of movement disorders. , 1-35.
CrossRef33
Ruth H. Walker, Hans H. Jung, Adrian Danek. 2011. Neuroacanthocytosis. , 141-151.
CrossRef34
I. Vansteenkiste, W. A. Gool, D. J. Hofstee, Marina A. J. Tijssen. (2011) Conversion disorder as initial diagnosis in pantothenate kinase associated neurodegeneration. Journal of Neurology 258:1, 152-154
CrossRef35
Rafael Fermin Delgado, Pedro Roa Sanchez, Herwin Speckter, Eddy Perez Then, Ramney Jimenez, Jairo Oviedo, Paulo R. Dellani, Bernd Foerster, Peter Stoeter. (2011) Missense PANK2 mutation without “Eye of the tiger” sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN). Journal of Magnetic Resonance Imagingn/a-n/a
CrossRef36
Susanne A. Schneider, John Hardy, Kailash P. Bhatia. (2011) Syndromes of neurodegeneration with brain iron accumulation (NBIA): An update on clinical presentations, histological and genetic underpinnings, and treatment considerations. Movement Disordersn/a-n/a
CrossRef37
Sumimasa Yamashita. (2010) An 8-year-old boy with gait disturbance and the rapid increase of muscle tonus. Neuropathology 30:6, 661-664
CrossRef38
Amaryllis Van Craenenbroeck, Marilien Gebruers, Jean-Jacques Martin, Patrick Cras. (2010) Hallervorden-Spatz disease: Historical case presentation in the spotlight of nosological evolution. Movement Disorders 25:15, 2486-2492
CrossRef39
Susanne A. Schneider, Kailash P. Bhatia. (2010) Rare Causes of Dystonia Parkinsonism. Current Neurology and Neuroscience Reports 10:6, 431-439
CrossRef40
Dinesh Rakheja, Naseem Uddin, Midori Mitui, Sandy Cope-Yokoyama, Robert N. Hogan, Dennis K. Burns. (2010) Fetal Akinesia Deformation Sequence and Neuroaxonal Dystrophy without PLA2G6 Mutation. Pediatric and Developmental Pathology 13:6, 492-496
CrossRef41
Brenda J. Polster, Shawn K. Westaway, Thuy M. Nguyen, Moon Y. Yoon, Susan J. Hayflick. (2010) Discordant expression of miR-103/7 and pantothenate kinase host genes in mouse. Molecular Genetics and Metabolism 101:2-3, 292-295
CrossRef42
Maura Poli, Manuela Derosas, Sara Luscieti, Patrizia Cavadini, Alessandro Campanella, Rosanna Verardi, Dario Finazzi, Paolo Arosio. (2010) Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron deregulation. Neurobiology of Disease 39:2, 204-210
CrossRef43
Annu Aggarwal, Susanne A. Schneider, Henry Houlden, Monty Silverdale, Reema Paudel, Coro Paisan-Ruiz, Shrinivas Desai, Mihir Munshi, Darshana Sanghvi, John Hardy, Kailash P. Bhatia, Mohit Bhatt. (2010) Indian-subcontinent NBIA: Unusual phenotypes, novel PANK2 mutations, and undetermined genetic forms. Movement Disorders 25:10, 1424-1431
CrossRef44
S. A. Schneider, K. P. Bhatia. (2010) Secondary dystonia - clinical clues and syndromic associations. European Journal of Neurology 17, 52-57
CrossRef45
Coro Paisán-Ruiz, Abi Li, Susanne A. Schneider, Janice L. Holton, Robert Johnson, Desmond Kidd, Jeremy Chataway, Kailash P. Bhatia, Andrew J. Lees, John Hardy, Tamas Revesz, Henry Houlden. (2010) Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. Neurobiology of Aging
CrossRef46
Susanne A. Schneider, Coro Paisan-Ruiz, Niall P. Quinn, Andrew J. Lees, Henry Houlden, John Hardy, Kailash P. Bhatia. (2010) ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. Movement Disorders 25:8, 979-984
CrossRef47
Daniel Johnstone, Elizabeth A. Milward. (2010) Molecular genetic approaches to understanding the roles and regulation of iron in brain health and disease. Journal of Neurochemistry
CrossRef48
Jae-Hyeok Lee, Dae-Seong Kim, Seung-Kug Baik, Sang-Ook Nam. (2010) Nigropallidal iron accumulation in pantothenate kinase-associated neurodegeneration demonstrated by susceptibility-weighted imaging. Journal of Neurology 257:4, 661-662
CrossRef49
Hiroshi Doi, Shigeru Koyano, Satoko Miyatake, Naomichi Matsumoto, Tomoaki Kameda, Atsuko Tomita, Yosuke Miyaji, Yume Suzuki, Yukio Sawaishi, Yoshiyuki Kuroiwa. (2010) Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: Clinical features and 99mTc-ECD brain perfusion SPECT findings. Journal of the Neurological Sciences 290:1-2, 172-176
CrossRef50
L. Timmermann, K. A. M. Pauls, K. Wieland, R. Jech, G. Kurlemann, N. Sharma, S. S. Gill, C. A. Haenggeli, S. J. Hayflick, P. Hogarth, K. L. Leenders, P. Limousin, C. J. Malanga, E. Moro, J. L. Ostrem, F. J. Revilla, P. Santens, A. Schnitzler, S. Tisch, F. Valldeoriola, J. Vesper, J. Volkmann, D. Woitalla,, S. Peker. (2010) Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation. Brain 133:3, 701-712
CrossRef51
R. Awasthi, R.K. Gupta, R. Trivedi, J.K. Singh, V.K. Paliwal, R.K.S. Rathore. (2010) Diffusion Tensor MR Imaging in Children with Pantothenate Kinase-Associated Neurodegeneration with Brain Iron Accumulation and Their Siblings. American Journal of Neuroradiology 31:3, 442-447
CrossRef52
Jerzy Szumowski, Erhan Bas, Kirsten Gaarder, Erwin Schwarz, Deniz Erdogmus, Susan Hayflick. (2010) Measurement of brain iron distribution in Hallevorden-Spatz syndrome. Journal of Magnetic Resonance Imaging 31:2, 482-489
CrossRef53
Helen Ling, Andrew J. Lees. (2010) How Can Neuroimaging Help in the Diagnosis of Movement Disorders?. Neuroimaging Clinics of North America 20:1, 111-123
CrossRef54
R.W. Orrell. 2010. Hypoprebetalipoproteinemia, Acanthocytosis, Retinitis Pigmentosa, and Pallidal Degeneration (HARP Syndrome). , 59-61.
CrossRef55
S.J. Hayflick. 2010. Hallervorden–Spatz Syndrome (PKAN). , 1-3.
CrossRef56
S.J. Hayflick. 2010. Eye-of-the-Tiger Sign. , 471-472.
CrossRef57
Harvey S. Singer, Jonathan W. Mink, Donald L. Gilbert, Joseph Jankovic. 2010. Inherited Metabolic Disorders Associated with Extrapyramidal Symptoms. , 164-204.
CrossRef58
Maria Bozi, Mar Matarin, Ioannis Theocharis, Costas Potagas, Leonidas Stefanis. (2009) A patient with pantothenate kinase-associated neurodegeneration and supranuclear gaze palsy. Clinical Neurology and Neurosurgery 111:8, 688-690
CrossRef59
Z. Wu, C. Li, S. Lv, B. Zhou. (2009) Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model. Human Molecular Genetics 18:19, 3659-3672
CrossRef60
L. Zamarian, T. Bodner, S. K. Revkin, T. Benke, S. Boesch, E. Donnemiller, M. Delazer. (2009) Numerical deficits in a single case of basal ganglia dysfunction. Neurocase 15:5, 390-404
CrossRef61
Ronen Spiegel, Avraham Shaag, Simon Edvardson, Hanna Mandel, Polina Stepensky, Stavit A. Shalev, Yoseph Horovitz, Ophry Pines, Orly Elpeleg. (2009) SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis. Annals of Neurology 66:3, 419-424
CrossRef62
Alexander Frizell Santillo, Lena Skoglund, Maria Lindau, Karin Edebol Eeg-Olofsson, Metin Tovi, Henry Engler, Rose-Marie Brundin, Sofie Ingvast, Lars Lannfelt, Anna Glaser, Lena Kilander. (2009) Frontotemporal Dementia-amyotrophic Lateral Sclerosis Complex is Simulated by Neurodegeneration With Brain Iron Accumulation. Alzheimer Disease & Associated Disorders 23:3, 298-300
CrossRef63
Roongroj Bhidayasiri, Stefan-M. Pulst. (2009) Juvenile parkinsonism. European Journal of Paediatric Neurology 13:3, 290-292
CrossRef64
Yih-Ru Wu, Chiung-Mei Chen, Chih-Ying Chao, Ron-Kuo Lyu, Guey-Jen Lee-Chen. (2009) Pantothenate kinase-associated neurodegeneration in two Taiwanese siblings: Identification of a novel PANK2 gene mutation. Movement Disorders 24:6, 940-941
CrossRef65
Susanne A. Schneider, Kailash P. Bhatia, John Hardy. (2009) Complicated recessive dystonia parkinsonism syndromes. Movement Disorders 24:4, 490-499
CrossRef66
T. Cabada Giadás, M. Cristina Caballero Martínez, Carmen Echávarri Zalba, S. Solchaga Álvarez, M.C. Bacaicoa Saralegui. (2009) Actualización radiopatológica en demencias. Resonancia magnética posmortem. Radiología 51:2, 127-139
CrossRef67
S. Sachin, V. Goyal, S. Singh, G. Shukla, M.C. Sharma, S. Gaikwed, M. Behari. (2009) Clinical spectrum of Hallervorden-Spatz syndrome in India. Journal of Clinical Neuroscience 16:2, 253-258
CrossRef68
Shinji Saiki, Takeshi Sekine, Yuji Ueno, Hiroyo Yoshino, Junko Takahashi, Yoshihiko Tani, Yasunori Kambe, Yumiko Motoi, Nobutaka Hattori. (2009) An adult-onset case of idiopathic neurodegeneration with brain iron accumulation without mutations in the PANK2 and PLA2G6 genes. Rinsho Shinkeigaku 49:8, 474-478
CrossRef69
Coro Paisan-Ruiz, Kailash P. Bhatia, Abi Li, Dena Hernandez, Mary Davis, Nick W. Wood, John Hardy, Henry Houlden, Andrew Singleton, Susanne A. Schneider. (2009) Characterization of PLA2G6 as a locus for dystonia-parkinsonism. Annals of Neurology 65:1, 19-23
CrossRef70
Young-Kyung Sunwoo, Jeong-Seop Lee, Won-Hyoung Kim, Yong-Bum Shin, Myung-Ji Lee, In-Hee Cho, Sun-Myeong Ock. (2009) Psychiatric Disorder in Two Siblings with Hallervorden-Spatz Disease. Psychiatry Investigation 6:3, 226
CrossRef71
Mohamad A. Mikati, Amin Yehya, Houssein Darwish, Pascale Karam, Youssef Comair. (2009) Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration. European Journal of Paediatric Neurology 13:1, 61-64
CrossRef72
Joo-Hyun Seo, Sook-Keun Song, Phil Hyu Lee. (2009) A Novel PANK2 Mutation in a Patient with Atypical Pantothenate-Kinase-Associated Neurodegeneration Presenting with Adult-Onset Parkinsonism. Journal of Clinical Neurology 5:4, 192
CrossRef73
C.-H. Lee, C.-C. Wu, Y.-N. Wu, H.-S. Chiang. (2008) Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens. Human Reproduction 24:3, 748-755
CrossRef74
Ruma Banerjee, Victor Vitvitsky, Sanjay K. Garg. (2008) The undertow of sulfur metabolism on glutamatergic neurotransmission. Trends in Biochemical Sciences 33:9, 413-419
CrossRef75
Jeremy J. Moeller, Robert J. B. Macaulay, Paul N. Valdmanis, Lyle E. Weston, Guy A. Rouleau, Nicolas Dupré. (2008) Autosomal dominant sensory ataxia: a neuroaxonal dystrophy. Acta Neuropathologica 116:3, 331-336
CrossRef76
F. Sedel, J.-M. Saudubray, E. Roze, Y. Agid, M. Vidailhet. (2008) Movement disorders and inborn errors of metabolism in adults: A diagnostic approach. Journal of Inherited Metabolic Disease 31:3, 308-318
CrossRef77
Ilka Haase, Markus Fischer, Adelbert Bacher, Wolfgang Eisenreich, Felix Rohdich. 2008. Cofactor Biosynthesis. .
CrossRef78
Grant A Mitchell, Nicolas Gauthier, Alain Lesimple, Shu Pei Wang, Orval Mamer, Ijaz Qureshi. (2008) Hereditary and acquired diseases of acyl-coenzyme A metabolism. Molecular Genetics and Metabolism 94:1, 4-15
CrossRef79
Gian Luca Forni, Manuela Balocco, Laura Cremonesi, Giovanni Abbruzzese, Roberto Carlo Parodi, Roberta Marchese. (2008) Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation. Movement Disorders 23:6, 904-907
CrossRef80
Sun J. Chung, Jae-Hong Lee, Myoung C. Lee, Han-Wook Yoo, Gu-Hwan Kim. (2008) Focal hand dystonia in a patient with PANK2 mutation. Movement Disorders 23:3, 466-468
CrossRef81
Chul Hyoung Lyoo, Holger Prokisch, Thomas Meitinger, Seung Yeob Lee, Do Hyoun Kim, Myung Sik Lee. (2008) Anticholinergic-responsive gait freezing in a patient with pantothenate kinase-associated neurodegeneration. Movement Disorders 23:2, 283-284
CrossRef82
Donald C. Shields, Nutan Sharma, John T. Gale, Emad N. Eskandar. (2007) Pallidal Stimulation for Dystonia in Pantothenate Kinase-associated Neurodegeneration. Pediatric Neurology 37:6, 442-445
CrossRef83
K. Strecker, S. Hesse, F. Wegner, O. Sabri, J. Schwarz, J.-P. Schneider. (2007) Eye of the Tiger sign in multiple system atrophy. European Journal of Neurology 14:11, e1-e2
CrossRef84
Danish Saleheen, Tuba Ali, Zarmeneh Aly, Bhojo Khealani, Philippe M. Frossard. (2007) Novel Mutation in the PANK2 Gene Leads to Pantothenate Kinase-Associated Neurodegeneration in a Pakistani Family. Pediatric Neurology 37:4, 296-298
CrossRef85
Ya Ke, Zhong Ming Qian. (2007) Brain iron metabolism: Neurobiology and neurochemistry. Progress in Neurobiology 83:3, 149-173
CrossRef86
Susanne A Schneider, Ruth H Walker, Kailash P Bhatia. (2007) The Huntington's disease-like syndromes: what to consider in patients with a negative Huntington's disease gene test. Nature Clinical Practice Neurology 3:9, 517-525
CrossRef87
H. H. Jung, A. Danek, B. M. Frey. (2007) McLeod syndrome: a neurohaematological disorder. Vox Sanguinis 93:2, 112-121
CrossRef88
Erik Madsen, Jonathan D. Gitlin. (2007) Copper and Iron Disorders of the Brain. Annual Review of Neuroscience 30:1, 317-337
CrossRef89
Y. M. Kuo, S. J. Hayflick, J. Gitschier. (2007) Deprivation of pantothenic acid elicits a movement disorder and azoospermia in a mouse model of pantothenate kinase-associated neurodegeneration. Journal of Inherited Metabolic Disease 30:3, 310-317
CrossRef90
K. Freeman, A. Gregory, A. Turner, P. Blasco, P. Hogarth, S. Hayflick. (2007) Intellectual and adaptive behaviour functioning in pantothenate kinase-associated neurodegeneration. Journal of Intellectual Disability Research 51:6, 417-426
CrossRef91
Marios Panas, Konstantinos Spengos, Georgios Koutsis, Georgios Tsivgoulis, Konstantinos Sfagos, Nikolaos Kalfakis, Dimitris Vassilopoulos. (2007) Psychosis as presenting symptom in adult-onset Hallervorden-Spatz syndrome. Acta Neuropsychiatrica 19:2, 122-124
CrossRef92
Ruth H. Walker, Adrian Danek, Carol Dobson-Stone, Renzo Guerrini, Hans H. Jung, Anne-Louise Lafontaine, Luca Rampoldi, François Tison, Eva Andermann. (2006) Developments in neuroacanthocytosis: Expanding the spectrum of choreatic syndromes. Movement Disorders 21:11, 1794-1805
CrossRef93
Arif Dalvi, Kelly E. Lyons, Rajesh Pahwa. 2006. Secondary Dystonia. , 245-266.
CrossRef94
Ruth H. Walker, Kevin StP. McNaught, Daniel P. Perl. 2006. Pathology of the Dystonias. , 65-92.
CrossRef95
M.M. Matarin, A.B. Singleton, H. Houlden. (2006) PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease. Neuroscience Letters 407:2, 162-165
CrossRef96
Howard L Geyer, Susan B Bressman. (2006) The diagnosis of dystonia. The Lancet Neurology 5:9, 780-790
CrossRef97
Zarazuela Zolkipli, Hisham Dahmoush, Dawn E. Saunders, W. K. Kling Chong, Robert Surtees. (2006) Pantothenate kinase 2 mutation with classic pantothenate-kinase-associated neurodegeneration without ‘eye-of-the-tiger’ sign on MRI in a pair of siblings. Pediatric Radiology 36:8, 884-886
CrossRef98
Neil V Morgan, Shawn K Westaway, Jenny E V Morton, Allison Gregory, Paul Gissen, Scott Sonek, Hakan Cangul, Jason Coryell, Natalie Canham, Nardo Nardocci, Giovanna Zorzi, Shanaz Pasha, Diana Rodriguez, Isabelle Desguerre, Amar Mubaidin, Enrico Bertini, Richard C Trembath, Alessandro Simonati, Carolyn Schanen, Colin A Johnson, Barbara Levinson, C Geoffrey Woods, Beth Wilmot, Patricia Kramer, Jane Gitschier, Eamonn R Maher, Susan J Hayflick. (2006) PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. Nature Genetics 38:7, 752-754
CrossRef99
P BINDU, S DESAI, K SHEHANAZ, M NETHRAVATHY, P PAL. (2006) Clinical heterogeneity in Hallervorden-Spatz syndrome: A clinicoradiological study in 13 patients from South India. Brain and Development 28:6, 343-347
CrossRef100
Jochen Hinkelbein, Armin Kalenka, Markus Alb. (2006) Anesthesia for patients with pantothenate-kinase-associated neurodegeneration (Hallervorden-Spatz disease) ? a literature review. Acta Neuropsychiatrica 18:3-4, 168-172
CrossRef101
Tsao-Wei Liang, Adam C. Truax, John Q. Trojanowski, Virginia M.-Y. Lee, Matthew B. Stern, Paul T. Kotzbauer. (2006) Partial deficit of pantothenate kinase 2 catalytic activity in a case of tremor-predominant neurodegeneration with brain iron accumulation. Movement Disorders 21:5, 718-722
CrossRef102
Angelo Antonini, Stefano Goldwurm, Riccardo Benti, Holger Prokisch, Monika Ebhardt, Roberto Cilia, Michela Zini, Andrea Righini, Giovanni Cossu, Gianni Pezzoli. (2006) Genetic, clinical, and imaging characterization of one patient with late-onset, slowly progressive, pantothenate kinase-associated neurodegeneration. Movement Disorders 21:3, 417-418
CrossRef103
Paola Valentino, Grazia Annesi, Innocenza C. Cirò Candiano, Ferdinanda Annesi, Donatella Civitelli, Patrizia Tarantino, Francesco Naso, Patrizia Spadafora, Sara Carrideo, Elvira V. De Marco, Domenico Consoli, Mario Zappia, Antonio Gambardella, Aldo Quattrone. (2006) Genetic heterogeneity in patients with pantothenate kinase–associated neurodegeneration and classic magnetic resonance imaging eye-of-the-tiger pattern. Movement Disorders 21:2, 252-254
CrossRef104
Monika B. Hartig, Konstanze Hörtnagel, Barbara Garavaglia, Giovanna Zorzi, Tomasz Kmiec, Thomas Klopstock, Kevin Rostasy, Marina Svetel, Vladimir S. Kostic, Markus Schuelke, Evelyn Botz, Adolf Weindl, Ivana Novakovic, Nardo Nardocci, Holger Prokisch, Thomas Meitinger. (2006) Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Annals of Neurology 59:2, 248-256
CrossRef105
John F. Schenck, Earl A. Zimmerman, Zhu Li, Sudeshna Adak, Angshuman Saha, Reeti Tandon, Kenneth M. Fish, Clifford Belden, Robert W. Gillen, Anne Barba, David L. Henderson, William Neil, Timothy O'Keefe. (2006) High-field Magnetic Resonance Imaging of Brain Iron in Alzheimer Disease. Topics in Magnetic Resonance Imaging 17:1, 41-50
CrossRef106
M. Tariq Bhatti. (2006) Retinitis pigmentosa, pigmentary retinopathies, and neurologic diseases. Current Neurology and Neuroscience Reports 6:5, 403-413
CrossRef107
Juan J. Zarranz, Juan C. Gómez-Esteban, Begoña Atarés, Elena Lezcano, Maribel Forcadas. (2006) Tau-predominant-associated pathology in a sporadic late-onset Hallervorden-Spatz syndrome. Movement Disorders 21:1, 107-111
CrossRef108
Y. Yang, Z. Wu, Y. M. Kuo, B. Zhou. (2005) Dietary rescue of fumble—a Drosophila model for pantothenate-kinase-associated neurodegeneration. Journal of Inherited Metabolic Disease 28:6, 1055-1064
CrossRef109
P. Rump, H. H. Lemmink, C. C. Verschuuren-Bemelmans, P. M. Grootscholten, J. M. Fock, S. J. Hayflick, S. K. Westaway, Y. J. Vos, A. J. Essen. (2005) A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect. Neurogenetics 6:4, 201-207
CrossRef110
David R. Williams, Ali Hadeed, Amir S. Najim al-Din, Abdel-Latif Wreikat, Andrew J. Lees. (2005) Kufor Rakeb Disease: Autosomal recessive, levodopa-responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia. Movement Disorders 20:10, 1264-1271
CrossRef111
Adrian Danek, Ruth H Walker. (2005) Neuroacanthocytosis. Current Opinion in Neurology 18:4, 386-392
CrossRef112
Robert A. Egan, Richard G. Weleber, Penelope Hogarth, Allison Gregory, Jason Coryell, Shawn K. Westaway, Jane Gitschier, Soma Das, Susan J. Hayflick. (2005) Neuro-Ophthalmologic and Electroretinographic Findings in Pantothenate Kinase-Associated Neurodegeneration (formerly Hallervorden-Spatz Syndrome). American Journal of Ophthalmology 140:2, 267.e1-267.e9
CrossRef113
Yu-hu Zhang, Bei-sha Tang, Ai-ling Zhao, Kun Xia, Zhi-gao Long, Ji-feng Guo, Shawn K. Westaway, Susan J. Hayflick. (2005) Novel compound heterozygous mutations in thePANK2 gene in a Chinese patient with atypical pantothenate kinase-associated neurodegeneration. Movement Disorders 20:7, 819-821
CrossRef114
Anthony P. Nicholas, Kelly S. Earnst, Daniel C. Marson. (2005) Atypical Hallervorden-Spatz disease with preserved cognition and obtrusive obsessions and compulsions. Movement Disorders 20:7, 880-886
CrossRef115
Marie Vidailhet, Pierre Pollak. (2005) Deep brain stimulation for dystonia: Make the lame walk. Annals of Neurology 57:5, 613-614
CrossRef116
Milan Hájek, Miriam Adamovičová, Vít Herynek, Antonín Škoch, Filip Jírů, Anna Křepelová, Monika Dezortová. (2005) MR relaxometry and 1H MR spectroscopy for the determination of iron and metabolite concentrations in PKAN patients. European Radiology 15:5, 1060-1068
CrossRef117
Pierre Castelnau, Laura Cif, Enza Maria Valente, Nathalie Vayssiere, Simone Hemm, Amandine Gannau, Annalisa DiGiorgio, Philippe Coubes. (2005) Pallidal stimulation improves pantothenate kinase-associated neurodegeneration. Annals of Neurology 57:5, 738-741
CrossRef118
James Connor, Domingo Pinero. 2005. Iron and Brain Function. .
CrossRef119
Seema Kapoor, Konstanze Hörtnagel, Siddhartha Gogia, Ritu Paul, Vishal Malhotra, Anjali Prakash. (2005) Pantothenate kinase associated neurodegeneration (Hallervorden — Spatz syndrome). The Indian Journal of Pediatrics 72:3, 261-263
CrossRef120
Adrian Danek, Hans H. Jung, Mariarosa A.B. Melone, Luca Rampoldi, Vania Broccoli, Ruth H. Walker. (2005) Neuroacanthocytosis: new developments in a neglected group of dementing disorders. Journal of the Neurological Sciences 229-230, 171-186
CrossRef121
Cecilia Marelli, Sylvie Piacentini, Barbara Garavaglia, Floriano Girotti, Alberto Albanese. (2005) Clinical and neuropsychological correlates in two brothers with pantothenate kinase-associated neurodegeneration. Movement Disorders 20:2, 208-212
CrossRef122
Pablo Mir, Mark J. Edwards, Andrew R.J. Curtis, Kailash P. Bhatia, Niall P. Quinn. (2005) Adult-onset generalized dystonia due to a mutation in the neuroferritinopathy gene. Movement Disorders 20:2, 243-245
CrossRef123
Douglas E. Crompton, Patrick F. Chinnery, David Bates, Timothy J. Walls, Margaret J. Jackson, Andrew J. Curtis, John Burn. (2005) Spectrum of movement disorders in neuroferritinopathy. Movement Disorders 20:1, 95-99
CrossRef124
Daniel G Healy, Patrick M Abou-Sleiman, Nicholas W Wood. (2004) PINK, PANK, or PARK? A clinicians' guide to familial parkinsonism. The Lancet Neurology 3:11, 652-662
CrossRef125
John F. Schenck, Earl A. Zimmerman. (2004) High-field magnetic resonance imaging of brain iron: birth of a biomarker?. NMR in Biomedicine 17:7, 433-445
CrossRef126
Satoshi Yamashita, Yasushi Maeda, Hiroyuki Ohmori, Yuji Uchida, Teruyuki Hirano, Kiminobu Yonemura, Eiichiro Uyama, Makoto Uchino. (2004) Pantothenate kinase-associated neurodegeneration initially presenting as postural tremor alone in a Japanese family with homozygous N245S substitutions in the pantothenate kinase gene. Journal of the Neurological Sciences 225:1-2, 129-133
CrossRef127
Madhavi Thomas, Joseph Jankovic. (2004) Neurodegenerative disease and iron storage in the brain. Current Opinion in Neurology 17:4, 437-442
CrossRef128
TORBEN MOOS, EVAN H. MORGAN. (2004) The Metabolism of Neuronal Iron and Its Pathogenic Role in Neurological Disease: Review. Annals of the New York Academy of Sciences 1012:1, 14-26
CrossRef129
Dominic C. Paviour, Robert A.H. Surtees, Andrew J. Lees. (2004) Diagnostic considerations in juvenile parkinsonism. Movement Disorders 19:2, 123-135
CrossRef130
Madhavi Thomas, Susan J. Hayflick, Joseph Jankovic. (2004) Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration. Movement Disorders 19:1, 36-42
CrossRef131
Pierre Pollank. (2004) Movement disorders: Parkinson's disease dominates. The Lancet Neurology 3:1, 15
CrossRef132
Susan J. Hayflick. (2003) Unraveling the Hallervorden-Spatz syndrome: pantothenate kinase???associated neurodegeneration is the name . . .. Current Opinion in Pediatrics 15:6, 572-577
CrossRef133
O. Oner, P. Oner, G. Deda, D. Icagasioglu. (2003) Psychotic disorder in a case with Hallervorden-Spatz disease. Acta Psychiatrica Scandinavica 108:5, 394-397
CrossRef134
Pasquale F. Finelli, Francis J. DiMario. (2003) Diagnostic Approach in Patients with Symmetric Imaging Lesions of the Deep Gray Nuclei. The Neurologist 9:5, 250-261
CrossRef135
Shevell, Michael, . (2003) Hallervorden and History. New England Journal of Medicine 348:1, 3-4
Full Text
