Journal of Inherited Metabolic Disease

, Volume 23, Issue 8, pp 819–825 | Cite as

Tyrosine hydroxylase deficiency unresponsive to L-dopa treatment with unusual clinical and biochemical presentation

  • P. De Lonlay
  • M. C. Nassogne
  • A. H. van Gennip
  • A. C. van Cruchten
  • T. Billette de Villemeur
  • M. Cretz
  • C. Stoll
  • J. M. Launay
  • G. C. V. Steenberger-Spante
  • L. P. W. van den Heuvel
  • R. A. Wevers
  • J. M. Saudubray
  • N. G. G. M. Abeling
Article

Abstract

Tyrosine hydroxylase (TH) deficiency is generally considered as a cause of the autosomal recessive form of dopa-responsive dystonia, also known as Segawa disease. Clinical hallmarks comprise parkinsonian and other extrapyramidal symptoms. Biochemically the defect leads to the defective synthesis of catecholamines, in particular dopamine. The diagnosis relies on a characteristic pattern of biogenic amine metabolites exclusively in the CSF and can be confirmed by establishing a mutation in the TH gene. Here we present a patient meeting all diagnostic criteria, including a new homozygous mutation (926T>C) with confirmed parental heterozygosity, extrapyramidal symptoms, but atypical other symptoms with periodic neurological episodes observed every 4 days and unresponsive to dopa treatment. The CSF biochemical abnormalities were severe. Uncharacteristically, a strongly abnormal urinary catecholamine metabolite pattern was also consistently observed. The atypical presentation of this patient shows that the clinical and metabolic phenotype of TH deficiency is more variable than formerly thought, and that the condition should no longer be considered as a treatable disorder per se.

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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • P. De Lonlay
    • 1
  • M. C. Nassogne
    • 1
  • A. H. van Gennip
    • 2
    • 3
  • A. C. van Cruchten
    • 2
    • 3
  • T. Billette de Villemeur
    • 4
  • M. Cretz
    • 5
  • C. Stoll
    • 6
  • J. M. Launay
    • 7
  • G. C. V. Steenberger-Spante
    • 2
    • 3
  • L. P. W. van den Heuvel
    • 2
    • 3
  • R. A. Wevers
    • 2
    • 3
  • J. M. Saudubray
    • 1
  • N. G. G. M. Abeling
    • 2
    • 3
  1. 1.Départment de PédiatrieHôpital Necker-Enfants MaladesFrance
  2. 2.Academic Medical CenterUniversity of AmsterdamNetherlands
  3. 3.Departments of Clinical ChemistryEmma Children's HospitalAmsterdamThe Netherlands
  4. 4.Service de Neurologie PédiatriqueHôpital TrousseauFrance
  5. 5.Service de PédiatrieHôpital de ColmarColmarFrance
  6. 6.Service de GénétiqueStrasbourg
  7. 7.Service de BiochimieHôpital LariboisièreParis

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