Tyrosine Hydroxylase Deficiency Presenting with a Biphasic Clinical Course

Abstract

Tyrosine hydroxylase deficiency, a cause of the autosomal recessive form of L-DOPA responsive dystonia, has been associated with a broad spectrum of movement disorders and clinical courses. We describe a new patient presenting with an early onset spastic paraplegia who later developed a progressive generalized dystonic-dyskinetic syndrome. He markedly improved with a very low dosage of L-DOPA/carbidopa, while higher dosages were not tolerated. Two novel mutations (p.G414R/p.L510Q) were detected in the TH gene.

Key words

tyrosine hydroxylase - biogenic amine disorders - spastic paraplegia - dystonic syndrome - L-DOPA/carbidopa

References

• 1 Bandmann O, Marsden CD, Wood NW. Atypical presentations of dopa-responsive dystonia.  Adv Neurol. 1998;  78 283-290
• 2 Dionisi-Vici C, Hoffmann GF, Leuzzi V, Hoffken H, Brautigam C, Rizzo C. et al . Tyrosine hydroxylase deficiency with severe clinical course: clinical and biochemical investigations and optimization of therapy.  J Pediatr. 2000;  136 560-562
• 3 Furukawa Y, Kish SJ, Fahn S. Dopa-responsive dystonia due to mild tyrosine hydroxylase deficiency.  Ann Neurol. 2004;  55 147-148
• 4 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
• 5 Goodwill KE, Sabatier C, Marks C, Raag R, Fitzpatrick PF, Stevens RC. Crystal structure of tyrosine hydroxylase at 2.3-angstrom and its implications for inherited neurodegenerative diseases.  Nature Struct Biol. 1997;  4 578-585
• 6 Grima B, Lamouroux A, Boni C, Julien JF, Javoy-Agid F, Mallet J. A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics.  Nature. 1987;  326 707-711
• 7 Hoffmann GF, Assmann B, Brautigam C, Dionisi-Vici C, Haussler M, Klerk JB de. et al . Tyrosine hydroxylase deficiency causes progressive encephalopathy and dopa-nonresponsive dystonia.  Ann Neurol. 2003;  54 ((Suppl 6)) S56-S65
• 8 Knappskog PM, Flatmark T, Mallet J, Ludecke B, Bartholome K. Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381 K) in the tyrosine hydroxylase gene.  Hum Mol Genet. 1995;  4 1209-1212
• 9 Ludecke B, Knappskog PM, Clayton PT, Surtees RAH, Clelland JD, Heales SJR. 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
• 10 Nardocci N, Zorzi G, Blau N, Fernandez Alvarez E, Sesta M, Angelini L. et al . Neonatal dopa-responsive extrapyramidal syndrome in twins with recessive GTPCH deficiency.  Neurology. 2003;  60 335-337

Correspondence