title: Dopa-responsive dystonia and Tourette syndrome in a large Danish family.
abstract: BACKGROUND
  Guanosine triphosphate cyclohydrolase I (GTPCH) catalyzes the first step in the synthesis of tetrahydrobiopterin (BH4). Autosomal dominantly inherited defects in the GTPCH gene (GCH1) cause a form of dystonia that is responsive to treatment with levodopa (dopa-responsive dystonia [DRD]).
  
  
  OBJECTIVE
  To investigate molecular and clinical aspects of DRD in a large Danish family.
  
  
  METHODS
  For analysis of the GCH1 gene, a mutation-scanning method based on denaturing gradient gel electrophoresis (DGGE) was used. A novel mutation, X251R, was identified in the GCH1 gene of 2 distantly related Danish patients with DRD, one of whom also had Tourette syndrome (TS). Thirty-five additional family members were investigated for this mutation, and 16 of them underwent clinical neurological examination.
  
  
  RESULTS
  A total of 18 patients were heterozygous for the X251R allele, 16 of whom had neurological complaints spanning from very mild parkinsonism to severe invalidism due to dystonia. Of 13 symptomatic heterozygotes who had been neurologically examined, 10 had signs of dystonia or parkinsonism. Sixteen of the heterozygotes were treated with levodopa, and 13 reported a treatment benefit. Three of the symptomatic heterozygotes had signs of TS.
  
  
  CONCLUSIONS
  This study confirms the large variability in DRD symptoms and emphasizes the usefulness of molecular analysis for diagnosis and treatment of DRD. The presence of TS is suggested to be coincidental, though the development of TS-like symptoms due to mutations in GCH1 cannot be excluded.
authors.affiliation: Department of Biochemistry, John F. Kennedy Institute, Glostrup, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Romstad
authors.forename: Erik
authors.initials: E
authors.lastname: Dupont
authors.forename: Bente
authors.initials: B
authors.lastname: Krag-Olsen
authors.forename: Karen
authors.initials: K
authors.lastname: Østergaard
authors.forename: Per
authors.initials: P
authors.lastname: Guldberg
authors.forename: Flemming
authors.initials: F
authors.lastname: Güttler
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D003718:Denmark / Q000208:ethnology; D015259:Dopamine Agents / Q000627:therapeutic use*; D004421:Dystonia / Q000175:diagnosis* / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D005879:Tourette Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*
chemical_list: D015259:Dopamine Agents; D007980:Levodopa