Molecular genetics of hereditary dystonia--mutations in the GTP cyclohydrolase I gene

Brain Res Bull. 1997;43(1):35-8. doi: 10.1016/s0361-9230(96)00353-x.


We found that mutations of GTP cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin, which is the cofactor of dopamine-synthesizing tyrosine hydroxylase, cause dominantly inherited hereditary progressive dystonia with marked diurnal fluctuation (HPD, Segawa's disease) probably owing to the decrease of dopamine in the basal ganglia. These results indicate that tyrosine hydroxylase in the nigrostriatal dopamine neurons may be most sensitive to tetrahydrobiopterin deficiency causing dystonia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Child
  • Dystonia / enzymology
  • Dystonia / genetics*
  • GTP Cyclohydrolase / deficiency
  • GTP Cyclohydrolase / genetics*
  • Genes, Dominant*
  • Genes, Recessive*
  • Humans
  • Mutation
  • Parkinson Disease / enzymology
  • Parkinson Disease / genetics
  • Tyrosine 3-Monooxygenase / genetics


  • Tyrosine 3-Monooxygenase
  • GTP Cyclohydrolase