A novel compound heterozygous tyrosine hydroxylase mutation (p.R441P) with complex phenotype

J Parkinsons Dis. 2011;1(1):119-22. doi: 10.3233/JPD-2011-11006.


Tyrosine hydroxylase (TH) is a tetrahydrobiopterin (BH4) dependent enzyme that catalyses the conversion of L-tyrosine to L-dopa, the rate-limiting step in the biosynthesis of dopamine. Autosomal recessive mutations in the TH gene cause impaired TH activity and are associated with phenotypes ranging from autosomal recessive dopa-responsive dystonia (DRD) to progressive infantile encephalopathy. Herein, we present a patient with TH-deficiency due to two compound heterozygous missense mutations in the TH/gene, one of which is novel (p.R441P). A clinical update on TH-deficiency and clues on how to achieve a timely diagnosis of this highly treatable disorder is provided.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Arginine / genetics
  • Heterozygote
  • Humans
  • Male
  • Mutation, Missense / genetics*
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology*
  • Phenotype
  • Proline / genetics
  • Tyrosine 3-Monooxygenase / deficiency
  • Tyrosine 3-Monooxygenase / genetics*


  • Arginine
  • Proline
  • Tyrosine 3-Monooxygenase