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Dopa-Responsive Dystonia

  • Yoshiaki Furukawa
  • Mark Guttman
  • Stephen J. Kish
Part of the Current Clinical Neurology book series (CCNEU)

Abstract

Patient 1: A 6-year-old girl with gait disturbance was introduced by an orthopedist in 1990, before the discovery of causative genes in dopa-responsive dystonia (DRD). Although early motor development was normal, she had Trendelenburg’s symptoms resulting from a congenital dislocation of the left hip (acetabular dysplasia). In addition, she developed flexion-inversion of the left foot at the age of 3 years, which became aggravated toward the evening and was alleviated in the morning after sleep. Her postural dystonia spread to other limbs within 3 years but was more pronounced in the legs. Neurological examination also revealed symmetric hyperreflexia without extensor plantar responses, and rigid hypertonicity in the legs. Investigations, including copper metabolism and brain magnetic resonance imaging, were normal. Therapeutic trials with levodopa and tetrahydrobiopterin (BH4; the cofactor for tyrosine hydroxylase) were considered, and a lumbar puncture was performed to measure cerebrospinal fluid (CSF) pterins. She remarkably responded to low doses of levodopa but not to acute BH4 administration. After increasing the dosage of levodopa (20 mg/kg/day, without a decarboxylase inhibitor [DCI]) and undergoing an operation (acetabuloplasty) for the complicated condition, she became completely normal and was diagnosed as DRD. The diagnosis was supported by CSF data (decreased total biopterin and neopterin) and was confirmed later by genetic analysis (1,2).

Keywords

Tyrosine Hydroxylase Motor Delay Tyrosine Hydroxylase Gene Extensor Plantar Response DYT1 Dystonia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Furukawa Y, Nishi K, Kondo T, Mizuno Y, Narabayashi H. CSF biopterin levels and clinical features of patients with juvenile parkinsonism. Adv Neurol 1993;60:562–567.PubMedGoogle Scholar
  2. 2.
    Furukawa Y, Shimadzu M, Rajput AH, et al. GTP-cyclohydrolase I gene mutations in hereditary progressive and dopa-responsive dystonia. Ann Neurol 1996;39:609–617.PubMedCrossRefGoogle Scholar
  3. 3.
    Furukawa Y, Guttman M, Sparagana SP, et al. Dopa-responsive dystonia due to a large deletion in the GTP cyclohydrolase I gene. Ann Neurol 2000:47;517–520.PubMedCrossRefGoogle Scholar
  4. 4.
    Nygaard TG. Dopa-responsive dystonia: delineation of the clinical syndrome and clues to patho-genesis. Adv Neurol 1993;60:577–585.PubMedGoogle Scholar
  5. 5.
    Segawa M, Nomura Y. Hereditary progressive dystonia with marked diurnal fluctuation. In: Segawa M, ed. Hereditary progressive dystonia with marked diurnal fluctuation. Parthenon, New York, NY: 1993;3–19.Google Scholar
  6. 6.
    Nygaard TG, Snow BJ, Fahn S, Calne DB. Dopa-responsive dystonia: clinical characteristics and definition. In: Segawa M, ed. Hereditary progressive dystonia with marked diurnal fluctuation. Parthenon, New York, NY: 1993;21–35.Google Scholar
  7. 7.
    Furukawa Y, Kish SJ. Dopa-responsive dystonia: recent advances and remaining issues to be addressed. Mov Disord 1999:14;709–715.PubMedCrossRefGoogle Scholar
  8. 8.
    Furukawa Y, Mizuno Y, Narabayashi H. Early-onset parkinsonism with dystonia: clinical and biochemical differences from hereditary progressive dystonia or DOPA-responsive dystonia. Adv Neurol 1996;69:327–337.PubMedGoogle Scholar
  9. 9.
    Fahn S, Bressman SB, Marsden CD. Classification of dystonia. Adv Neurol 1998;78:1–10.PubMedGoogle Scholar
  10. 10.
    Nygaard TG, Wilhelmsen KC, Risch NJ, et al. Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q. Nat Genet 1993;5:386–391.PubMedCrossRefGoogle Scholar
  11. 11.
    Ichinose H, Ohye T, Takahashi E, et al. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nat Genet 1994;8:236–242.PubMedCrossRefGoogle Scholar
  12. 12.
    Tanaka H, Endo K, Tsuji S, et al. The gene for hereditary progressive dystonia with marked diurnal fluctuation maps to chromosome 14q. Ann Neurol 1995;37:405–408.PubMedCrossRefGoogle Scholar
  13. 13.
    Lüdecke B, Dworniczak B, Bartholomé K. A point mutation in the tyrosine hydroxylase gene associated with Segawa’s syndrome. Hum Genet 1995;95:123–125.PubMedGoogle Scholar
  14. 14.
    Grötzsch H, Pizzolato G-P, Ghika J, et al. Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT 14. Neurology 2002;58:1839–1842.PubMedGoogle Scholar
  15. 15.
    Furukawa Y, Rajput AH. Inherited myoclonus-dystonia: how many causative genes and clinical phenotypes? Neurology 2002;59:1130–1131.PubMedGoogle Scholar
  16. 16.
    Furukawa Y. Genetics and Biochemistry of dopa-responsive dystonia: significance of striatal tyrosine hydroxylase protein loss. Adv Neurol 2003;91:401–410.PubMedGoogle Scholar
  17. 17.
    Bartholomé K, Lüdecke B. Mutations in the tyrosine hydroxylase gene cause various forms of L-dopa-responsive dystonia. Adv Pharmacol 1998;42:48–49.PubMedGoogle Scholar
  18. 18.
    Swaans RJM, Rondot P, Renier WO, van den Heuvel LPWJ, Steenbergen-Spanjers GCH, Wevers RA. Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism. Ann Hum Genet 2000;64:25–31.PubMedCrossRefGoogle Scholar
  19. 19.
    Furukawa Y, Graf WD, Wong H, Shimadzu M, Kish SJ. Dopa-responsive dystonia simulating spastic paraplegia due to tyrosine hydroxylase (TH) gene mutations. Neurology 2001:56;260–263.PubMedGoogle Scholar
  20. 20.
    Segawa M, Ohmi K, Itoh S, Aoyama M, Hayakawa H. Childhood basal ganglia disease with remarkable response to L-DOPA: hereditary progressive basal ganglia disease with marked fluctuation. Shinryo 1971;24:667–672.Google Scholar
  21. 21.
    Castaigne P, Rondot P, Ribadeau-Dumas JL, Saïd G. Affection extrapyramidale évoluant chez deux jeunes frères: effets remarquables du traitement par la L-Dopa. Rev Neurol 1971;124:162–166.PubMedGoogle Scholar
  22. 22.
    Inagaki H, Ohye T, Suzuki T, et al. Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one allele in hereditary progressive dystonia with marked diurnal fluctuation. Biochem Biophys Res Commun 1999;260:747–751.PubMedCrossRefGoogle Scholar
  23. 23.
    Segawa M, Hosaka A, Miyagawa F, Nomura Y, Imai H. Hereditary progressive dystonia with marked diurnal fluctuation. Adv Neurol 1976;14:215–233.PubMedGoogle Scholar
  24. 24.
    Rondot P, Ziegler M. Dystonia-L-dopa responsive or juvenile parkinsonism? J Neurol Transm 1983;Suppl 19:273–281.Google Scholar
  25. 25.
    Rondot P, Aicardi J, Goutières F, Ziegler M. Dystonies dopa-sensibles. Rev Neurol 1992;148:680–686.PubMedGoogle Scholar
  26. 26.
    Segawa M. Hereditary progressive dystonia with marked diurnal fluctuation. Brain Dev 2000;22(Suppl 1):S65–S80.PubMedCrossRefGoogle Scholar
  27. 27.
    Müller K, Hömberg V, Lenard HG. Motor control in childhood onset dopa-responsive dystonia (Segawa syndrome). Neuropediatrics 1989;20:185–191.PubMedCrossRefGoogle Scholar
  28. 28.
    Duvoisin RC, Yahr MD, Lieberman J, Antunes J, Rhee S. The striatal foot. Trans Am Neurol Assoc 1972;97:267.Google Scholar
  29. 29.
    Nygaard TG, Marsden CD, Duvoisin RC. Dopa-responsive dystonia. Adv Neurol 1988;50:377–384.PubMedGoogle Scholar
  30. 30.
    Furukawa Y, Kish SJ, Bebin EM, et al. Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. Ann Neurol 1998;44:10–16.PubMedCrossRefGoogle Scholar
  31. 31.
    Nygaard TG, Duvoisin RC. Hereditary dystonia-parkinsonism syndrome of juvenile onset. Neurology 1986;36:1424–1428.PubMedGoogle Scholar
  32. 32.
    Furukawa Y, Nygaard TG, Gütlich M, et al. Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia. Neurology 1999;53:1032–1041.PubMedGoogle Scholar
  33. 33.
    Nygaard TG, Trugman JM, de Yebenes JG, Fahn S. Dopa-responsive dystonia: the spectrum of clinical manifestations in a large North American family. Neurology 1990;40:66–69.PubMedGoogle Scholar
  34. 34.
    Nygaard TG, Takahashi H, Heiman GA, Snow BJ, Fahn S, Calne DB. Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia. Ann Neurol 1992;32:603–608.PubMedCrossRefGoogle Scholar
  35. 35.
    Steinberger D, Weber Y, Korinthenberg R, et al. High penetrance and pronounced variation in expressivity of GCH1 mutations in five families with dopa-responsive dystonia. Ann Neurol 1998;43:634–639.PubMedCrossRefGoogle Scholar
  36. 36.
    Tassin J, Dürr A, Bonnet A-M, et al. Levodopa-responsive dystonia: GTP cyclohydrolase I or parkin mutations? Brain 2000;123:1112–1121.PubMedCrossRefGoogle Scholar
  37. 37.
    Hoenicka J, Vidal L, Godoy M, Ochoa JJ, de Yébenes JG. New nonsense mutation in the GTP-cyclohydrolase I gene in L-DOPA responsive dystonia-parkinsonism. Mov Disord 2001;16:364–366.PubMedCrossRefGoogle Scholar
  38. 38.
    Furukawa Y, Kapatos G, Haycock JW, et al. Brain biopterin and tyrosine hydroxylase in asymptomatic dopa-responsive dystonia. Ann Neurol 2002;51:637–641.PubMedCrossRefGoogle Scholar
  39. 39.
    Furukawa Y, Guttman M, Wong H, Farrell SA, Furtado S, Kish SJ. Serum prolactin in symptomatic and asymptomatic dopa-responsive dystonia due to a GCH1 mutation. Neurology 2003;61:269–270.PubMedGoogle Scholar
  40. 40.
    Grimes DA, Barclay CL, Duff J, Furukawa Y, Lang AE. Phenocopies in a large GCH1 mutation positive family with dopa responsive dystonia: confusing the picture? J Neurol Neurosurg Psychiatry 2002;72:801–804.PubMedCrossRefGoogle Scholar
  41. 41.
    Furukawa Y, Kish SJ. Influence of development and aging on brain biopterin: implications for dopa-responsive dystonia onset. Neurology 1998;51:632–634.PubMedGoogle Scholar
  42. 42.
    Fink JK, Filling-Katz MR, Barton NW, Macrae PR, Hallett M, Cohen WE. Treatable dystonia presenting as spastic cerebral palsy. Pediatrics 1988;82:137–138.PubMedGoogle Scholar
  43. 43.
    Boyd K, Patterson V. Dopa responsive dystonia: a treatable condition misdiagnosed as cerebral palsy. Br Med J 1989;298:1019–1020.Google Scholar
  44. 44.
    Nygaard TG, Waran SP, Levine RA, Naini AB, Chutorian AM. Dopa-responsive dystonia simulating cerebral palsy. Pediatr Neurol 1994;11:236–240.PubMedCrossRefGoogle Scholar
  45. 45.
    Patel K, Roskrow T, Davis JS, Heckmatt JZ. Dopa responsive dystonia. Arch Dis Child 1995;73:256–257.PubMedGoogle Scholar
  46. 46.
    Bandmann O, Nygaard TG, Surtees R, Marsden CD, Wood NW, Harding AE. Dopa-responsive dystonia in British patients: new mutations of the GTP-cyclohydrolase I gene and evidence for genetic heterogeneity. Hum Mol Genet 1996;5:403–406.PubMedCrossRefGoogle Scholar
  47. 47.
    Bandmann O, Valente EM, Holmans P, et al. Dopa-responsive dystonia: a clinical and molecular genetic study. Ann Neurol 1998;44:649–656.PubMedCrossRefGoogle Scholar
  48. 48.
    Brique S, Destée A, Lambert J-C, et al. A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form. NeuroReport 1999;10:487–491.PubMedCrossRefGoogle Scholar
  49. 49.
    Steinberger D, Topka H, Fischer D, Müller U. GCH1 mutation in a patient with adult-onset oromandibular dystonia. Neurology 1999;52:877–879.PubMedGoogle Scholar
  50. 50.
    Klein C, Hedrich K, Kabakçi K, et al. Exon deletions in the GCHI gene in two of four Turkish families with dopa-responsive dystonia. Neurology 2002;59:1783–1786.PubMedGoogle Scholar
  51. 51.
    Leuzzi V, Carducci CA, Carducci Cl, Cardona F, Artiola C, Antonozzi I. Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome. Neurology 2002;59:1241–1243.PubMedGoogle Scholar
  52. 52.
    Hahn H, Trant MR, Brownstein MJ, Harper RA, Milstien S, Butler IJ. Neurologic and psychiatric manifestations in a family with a mutation in exon 2 of the guanosine triphosphate-cyclohydrolase gene. Arch Neurol 2001;58:749–755.PubMedCrossRefGoogle Scholar
  53. 53.
    Furukawa Y, Kish SJ, Lang AE. Scoliosis in a dopa-responsive dystonia family with a mutation of the GTP cyclohydrolase I gene. Neurology 2000;54:2187.PubMedGoogle Scholar
  54. 54.
    Ichinose H, Ohye T, Matsuda Y, et al. Characterization of mouse and human GTP cyclohydrolase I genes: mutations in patients with GTP cyclohydrolase I deficiency. J Biol Chem 1995;270:10,062–10,071.PubMedCrossRefGoogle Scholar
  55. 55.
    Niederwieser A, Blau N, Wang M, Joller P, Atarés M, Cardesa-Garcia J. GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia. Eur J Pediatr 1984;141:208–214.PubMedCrossRefGoogle Scholar
  56. 56.
    Blau N, Ichinose H, Nagatsu T, Heizmann CW, Zacchello F, Burlina AB. A missense mutation in a patient with guanosine triphosphate cyclohydrolase I deficiency missed in the newborn screening program. J Pediatr 1995;126:401–405.PubMedCrossRefGoogle Scholar
  57. 57.
    Blau N, Barnes I, Dhondt JL. International database of tetrahydrobiopterin deficiencies. J Inherit Metab Dis 1996;19:8–14.PubMedCrossRefGoogle Scholar
  58. 58.
    Furukawa Y, Lang AE, Trugman JM, et al. Gender-related penetrance and de novo GTP-cyclohydrolase I gene mutations in dopa-responsive dystonia. Neurology 1998;50:1015–1020.PubMedGoogle Scholar
  59. 59.
    Nagatsu T, Ichinose H. Comparative studies on the structure of human tyrosine hydroxylase with those of the enzyme of various mammals. Comp Biochem Physiol 1991;98C:203–210.Google Scholar
  60. 60.
    Furukawa Y. Update on dopa-responsive dystonia: locus heterogeneity and biochemical features. Adv Neurol 2004;94:127–138.PubMedGoogle Scholar
  61. 61.
    Knappskog PM, Flatmark T, Mallet J, Lüdecke B, Bartholomé K. Recessively inheritedL-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene. Hum Mol Genet 1995;4:1209–1212.PubMedCrossRefGoogle Scholar
  62. 62.
    Lüdecke B, Knappskog PM, Clayton PT,et al. Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene. Hum Mol Genet 1996;5:1023–1028.PubMedCrossRefGoogle Scholar
  63. 63.
    Bräutigam C, Wevers RA, Jansen RJT, et al. Biochemical hallmarks of tyrosine hydroxylase deficiency. Clin Chem 1998;44:1897–1904.PubMedGoogle Scholar
  64. 64.
    Surtees R, Clayton P. Infantile parkinsonism-dystonia: tyrosine hydroxylase deficiency. Mov Disord 1998;13:350.CrossRefGoogle Scholar
  65. 65.
    van den Heuvel LPWJ, Luiten B, Smeitink JAM, et al. A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population. Hum Genet 1998;102:644–646.PubMedCrossRefGoogle Scholar
  66. 66.
    Bräutigam C, Steenbergen-Spanjers GCH, Hoffmann GF, et al. Biochemical and molecular genetic characteristics of the severe form of tyrosine hydroxylase deficiency. Clin Chem 1999;45:2073–2078.PubMedGoogle Scholar
  67. 67.
    Wevers RA, de Ruk-van Andel JF, Bräutigam C, et al. A review of biochemical and molecular genetic aspects of tyrosine hydroxylase deficiency including a novel mutation (291delC). J Inher Metab Dis 1999;22:364–373.PubMedCrossRefGoogle Scholar
  68. 68.
    de Lonlay P, Nassogne MC, van Gennip AH, et al. Tyrosine hydroxylase deficiency unresponsive to L-dopa treatment with unusual clinical and biochemical presentation. J Inherit Metab Dis 2000;23:819–825.CrossRefGoogle Scholar
  69. 69.
    de Rijk-van Andel JF, Gabreëls FJM, Geurtz B, et al. L-dopa-responsive infantile hypokinetic rigid parkinsonism due to tyrosine hydroxylase deficiency. Neurology 2000;55:1926–1928.PubMedGoogle Scholar
  70. 70.
    Dionisi-Vici C, Hoffmann GF, Leuzzi V, et al. Tyrosine hydroxylase deficiency with severe clinical course: clinical and biochemical investigations and optimization of therapy. J Pediatr 2000;136:560–562.PubMedCrossRefGoogle Scholar
  71. 71.
    Janssen RJRJ, Wevers RA, Häussler M, et al. A branch site mutation leading to aberrant splicing of the human tyrosine hydroxylase gene in a child with a severe extrapyramidal movement disorder. Ann Hum Genet 2000;64:375–382.PubMedCrossRefGoogle Scholar
  72. 72.
    Grattan-Smith PJ, Wevers RA, Steenbergen-Spanjers GC, Fung VSC, Earl J, Wilcken B. Tyrosine hydroxylase deficiency: clinical manifestations of catecholamine insufficiency in infancy. Mov Disord 2002;17:354–359.PubMedCrossRefGoogle Scholar
  73. 73.
    Rajput AH, Gibb WRG, Zhong XH, et al. Dopa-responsive dystonia: pathological and biochemical observations in a case. Ann Neurol 1994;35:396–402.PubMedCrossRefGoogle Scholar
  74. 74.
    Häussler M, Hoffmann GF, Wevers RA. L-dopa and selegiline for tyrosine hydroxylase deficiency. J Pediatr 2001;138:451–452.PubMedGoogle Scholar
  75. 75.
    LeWitt PA, Miller LP, Levine RA, et al. Tetrahydrobiopterin in dystonia: identification of abnormal metabolism and therapeutic trials. Neurology 1986;36:760–764.PubMedGoogle Scholar
  76. 76.
    Fink JK, Barton N, Cohen W, Lovenberg W, Burns RS, Hallett M. Dystonia with marked diurnal variation associated with biopterin deficiency. Neurology 1988;38:707–711.PubMedGoogle Scholar
  77. 77.
    Fujita S, Shintaku H. The pathogenesis of hereditary progressive dystonia with marked diurnal fluctuation (HPD) and a metabolic abnormality of pteridines. Kushiro J Med 1990;2:64–67.Google Scholar
  78. 78.
    Takahashi H, Levine RA, Galloway MP, Snow BJ, Calne DB, Nygaard TG. Biochemical and fluorodopa positron emission tomographic findings in an asymptomatic carrier of the gene for dopa-responsive dystonia. Ann Neurol 1994;35:354–356.PubMedCrossRefGoogle Scholar
  79. 79.
    Furukawa Y, Mizuno Y, Nishi K, Narabayashi H. A clue to the pathogenesis of dopa-responsive dystonia. Ann Neurol 1995;37:139–140.PubMedCrossRefGoogle Scholar
  80. 80.
    Furukawa Y, Shimadzu M, Hornykiewicz O, Kish SJ. Molecular and biochemical aspects of hereditary progressive and dopa-responsive dystonia. Adv Neurol 1998;78:267–282.PubMedGoogle Scholar
  81. 81.
    Hirano M, Imaiso Y, Ueno S. Differential splicing of the GTP cyclohydrolase I RNA in dopa-responsive dystonia. Biochem Biophys Res Commun 1997;234:316–319.PubMedCrossRefGoogle Scholar
  82. 82.
    Hibiya M, Ichinose H, Ozaki N, et al. Normal values and age-dependent changes in GTP cyclohydrolase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromatography. J Chromatogr B 2000;740:35–42.CrossRefGoogle Scholar
  83. 83.
    Bezin L, Nygaard TG, Neville JD, Shen H, Levine RA. Reduced lymphoblast neopterin detects GTP cyclohydrolase dysfunction in dopa-responsive dystonia. Neurology 1998;50:1021–1027.PubMedGoogle Scholar
  84. 84.
    Bonafé L, Thöny B, Leimbacher W, Kierat L, Blau N. Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts. Clin Chem 2001;47:477–485.PubMedGoogle Scholar
  85. 85.
    Hirano M, Yanagihara T, Ueno S. Dominant negative effect of GTP cyclohydrolase I mutations in dopa-responsive hereditary progressive dystonia. Ann Neurol 1998;44:365–371.PubMedCrossRefGoogle Scholar
  86. 86.
    Hirano M, Ueno S. Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia. Neurology 1999;52:182–184.PubMedGoogle Scholar
  87. 87.
    Hwu W-L, Chiou Y-W, Lai S-Y, Lee Y-M. Dopa-responsive dystonia is induced by a dominant-negative mechanism. Ann Neurol 2000;48:609–613.PubMedCrossRefGoogle Scholar
  88. 88.
    Suzuki T, Ohye T, Inagaki H, Nagatsu T, Ichinose H. Characterization of wild-type and mutants of recombinant human GTP cyclohydrolase I: relationship to etiology of dopa-responsive dystonia. J Neurochem 1999;73:2510–2516.PubMedCrossRefGoogle Scholar
  89. 89.
    Hyland K, Fryburg JS, Wilson WG, et al. Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic test. Neurology 1997;48:1290–1297.PubMedGoogle Scholar
  90. 90.
    Saunders-Pullman RJ, Raymond D, Hyland K, et al. Markers of disease in dopa-responsive-dystonia. Mov Disord 1998;13(Suppl 2):285.Google Scholar
  91. 91.
    Bandmann O, Goertz M, Zschocke J, et al. The phenylalanine loading test in the differential diagnosis of dystonia. Neurology 2003;60:700–702.PubMedGoogle Scholar
  92. 92.
    Davis MD, Ribeiro P, Tipper J, Kaufman S. ‘7-Tetrahydrobiopterin,’ a naturally occurring analogue of tetrahydrobiopterin, is a cofactor for and a potential inhibitor of the aromatic amino acid hydroxylases. Proc Natl Acad Sci USA 1992;89:10,109–10,113.PubMedCrossRefGoogle Scholar
  93. 93.
    Snow BJ, Nygaard TG, Takahashi H, Calne DB. Positron emission tomographic studies of dopa-responsive dystonia and early-onset idiopathic parkinsonism. Ann Neurol 1993;34:733–738.PubMedCrossRefGoogle Scholar
  94. 94.
    Turjanski N, Bhatia K, Burn DJ, Sawle GV, Marsden CD, Brooks DJ. Comparison of striatal 18F-dopa uptake in adult-onset dystonia-parkinsonism, Parkinson’s disease, and dopa-responsive dystonia. Neurology 1993;43:1563–1568.PubMedGoogle Scholar
  95. 95.
    Naumann M, Pirker W, Reiners K, Lange K, Becker G, Brücke T. [123I]β-CIT single-photon emission tomography in DOPA-responsive dystonia. Mov Disord 1997;12:448–451.PubMedCrossRefGoogle Scholar
  96. 96.
    Jeon BS, Jeong J-M, Park S-S, et al. Dopamine transporter density measured by [123I]β-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia. Ann Neurol 1998;43:792–800.PubMedCrossRefGoogle Scholar
  97. 97.
    Kishore A, Nygaard TG, de la Fuente-Fernandez R, et al. Striatal D2 receptors in symptomatic and asymptomatic carriers of dopa-responsive dystonia measured with [11C]-raclopride and positron-emission tomography. Neurology 1998;50:1028–1032.PubMedGoogle Scholar
  98. 98.
    O’Sullivan JD, Costa DC, Gacinovic S, Lees AJ. SPECT imaging of the dopamine transporter in juvenile-onset dystonia. Neurology 2001;56:266–267.PubMedGoogle Scholar
  99. 99.
    Künig G, Leenders KL, Antonini A, Vontobel P, Weindl A, Meinck HM. D2 receptor binding in dopa-responsive dystonia. Ann Neurol 1998;44:758–762.PubMedCrossRefGoogle Scholar
  100. 100.
    Hauf M, Cousin P, Solida A, Albanese A, Ghika J, Schorderet DF. A family with segmental dystonia: evidence for polymorphism in GTP cyclohydrolase I gene (GCH I). Mov Disord 2000;15(Suppl 3):154–155.Google Scholar
  101. 101.
    Furukawa Y, Hornykiewicz O, Fahn S, Kish SJ. Striatal dopamine in early-onset primary torsion dystonia with the DYT1 mutation. Neurology 2000;54:1193–1195.PubMedGoogle Scholar
  102. 102.
    Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease: pathophysiologic and clinical implications. N Engl J Med 1988;318:876–880.PubMedCrossRefGoogle Scholar
  103. 103.
    Hornykiewicz O. Biochemical aspects of Parkinson’s disease. Neurology 1998;51(Suppl 2):S2–S9.PubMedGoogle Scholar
  104. 104.
    Zhong X-H, Haycock JW, Shannak K, et al. Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson’s disease and dominantly inherited olivopontocerebellar atrophy. Mov Disord 1995;10:10–17.PubMedCrossRefGoogle Scholar
  105. 105.
    Wilson JM, Levey AI, Rajput A, et al. Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson’s disease. Neurology 1996;47:718–726.PubMedGoogle Scholar
  106. 106.
    Hyland K, Gunasekera RS, Engle T, Arnold LA. Tetrahydrobiopterin and biogenic amine metabolism in the hph-1 mouse. J Neurochem 1996;67:752–759.PubMedCrossRefGoogle Scholar
  107. 107.
    Sumi-Ichinose C, Urano F, Kuroda R, et al. Catecholamines and serotonin are differently regulated by tetrahydrobiopterin: a study from 6-pyruvoyltetrahydropterin synthase knockout mice. J Biol Chem 2001;276:41,150–41,160.PubMedCrossRefGoogle Scholar
  108. 108.
    Ihara M, Kohara N, Urano F, et al. Neuroleptic malignant syndrome with prolonged catatonia in a dopa-responsive dystonia patient. Neurology 2002;59:1102–1104.PubMedGoogle Scholar
  109. 109.
    Bonafé L, Thöny B, Penzien JM, Czarnecki B, Blau N. Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet 2001;69:269–277.PubMedCrossRefGoogle Scholar
  110. 110.
    Hyland K, Arnold LA, Trugman JM. Defects of biopterin metabolism and biogenic amine biosynthesis: clinical, diagnostic, and therapeutic aspects. Adv Neurol 1998;78:301–308.PubMedGoogle Scholar
  111. 111.
    Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998;392:605–608.PubMedCrossRefGoogle Scholar
  112. 112.
    Ozelius LJ, Hewett JW, Page CE, et al. The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nat Genet 1997;17:40–48.PubMedCrossRefGoogle Scholar
  113. 113.
    Nygaard TG, Marsden CD, Fahn S. Dopa-responsive dystonia: long-term treatment response and prognosis. Neurology 1991;41:174–181.PubMedGoogle Scholar
  114. 114.
    Steinberger D, Korinthenberg R, Topka H, et al. Dopa-responsive dystonia: mutation analysis of GCH1 and analysis of therapeutic doses of L-dopa. Neurology 2000;55:1735–1737.PubMedGoogle Scholar
  115. 115.
    Nygaard TG, Duvoisin RC. Hereditary progressive dystonia/dopa-responsive dystonia. In: Joseph AB, Young RR, eds. Movement Disorders in Neurology and Neuropsychiatry. 2nd ed. Blackwell Science, Malden, MA: 1999; 531–537.Google Scholar
  116. 116.
    Fink JK, Ravin P, Argoff CE, et al. Tetrahydrobiopterin administration in biopterin-deficient progressive dystonia with diurnal variation. Neurology 1989;39:1393–1395.PubMedGoogle Scholar
  117. 117.
    Kapatos G, Kaufman S. Peripherally administered reduced pterins do enter the brain. Science 1981;212:955–956.PubMedCrossRefGoogle Scholar
  118. 118.
    Kaufman S, Kapatos G, Mclnnes RR, Schulman JD, Rizzo WB. Use of tetrahydropterins in the treatment of hyperphenylalaninemia due to defective synthesis of tetrahydrobiopterin: evidence that peripherally administered tetrahydropterins enter the brain. Pediatrics 1982;70:376–380.PubMedGoogle Scholar
  119. 119.
    Kondo T, Miwa H, Furukawa Y, Mizuno Y, Narabayashi H. Tetrahydrobiopterin therapy for juvenile parkinsonism. In: Segawa M, ed. Hereditary progressive dystonia with marked diurnal fluctuation. Parthenon, New York, NY: 1993; 133–140.Google Scholar
  120. 120.
    Hoffmann GF, Assmann B, Bräutigam C, et al. Tyrosine hydroxylase deficiency causes progressive encephalopathy and dopa-nonresponsive dystonia. Ann Neurol 2003;54(Suppl 6):S56–S65.PubMedCrossRefGoogle Scholar
  121. 121.
    Furukawa Y, Kish SJ, Fahn S. Dopa-responsive dystonia due to mild tyrosine hydroxylase deficiency. Ann Neurol 2004;55:147–148.PubMedCrossRefGoogle Scholar
  122. 122.
    Furukawa Y, Filiano JJ, Kish SJ. Amantadine for levodopa-induced choreic dyskinesia in compound heterozygotes for GCH1 mutations. Mov Disord 2004;19:1256–1258.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Yoshiaki Furukawa
    • 1
  • Mark Guttman
    • 2
  • Stephen J. Kish
    • 2
  1. 1.Movement Disorders Research LaboratoryCentre for Addiction and Mental Health-Clarke DivisionTorontoCanada
  2. 2.Centre for Addiction and Mental Health-Clarke DivisionHuman Neurochemical Pathology LaboratoryTorontoCanada

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