title: Novel GCH-1 mutations and unusual long-lasting dyskinesias in Korean families with dopa-responsive dystonia.
abstract: OBJECTIVE
  To describe the long-term follow-up data of Korean patients with GTP cyclohydrolase (GTPCH) I deficient dopa-responsive dystonia (DRD) with novel mutations and unusual long-lasting dyskinesias.
  
  
  METHODS
  Clinical features and genetic testing results of GCH1 from 19 patients that included 4 families who have been followed-up for up to 25 years were analyzed.
  
  
  RESULTS
  GCH1 mutations were confirmed in all our symptomatic subjects including 3 novel point mutations. All the subjects except for one family had typical manifestations of autosomal dominant GTPCH-I deficient DRD including early childhood onset dystonia predominantly in the legs, marked diurnal variation, intact cognition, no other systemic symptoms, and excellent sustained response to levodopa. The one family who was the exception had two gene positive members of DRD and one with dopa-unresponsive cervical dystonia with negative GCH1 mutation. One family and a sporadic case had been reported as gene negative in a previous study, but they typically had preserved dopamine transporter binding and low neopterin levels in cerebrospinal fluids; thus, GCH-1 mutation had been highly suspected, which was now confirmed by repeating the genetic testing this time. An early childhood-onset patient developed choreiform dyskinesias right after administration of levodopa. The dyskinesia had lasted for more than 4 years regardless of the levodopa dosages and then subsided while maintaining levodopa.
  
  
  CONCLUSIONS
  This report emphasizes the usefulness of the neopterin level in cerebrospinal fluids and dopamine transporter imaging in the differential diagnosis of DRD syndromes and a possible mechanism of levodopa-induced-dyskinesia in early childhood onset case.
authors.affiliation: Department of Neurology, SMG-SNU Boramae Medical Center, Seoul, South Korea.
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hee Joon
authors.initials: HJ
authors.lastname: Yang
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Beom S
authors.initials: BS
authors.lastname: Jeon
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015259:Dopamine Agents / Q000627:therapeutic use; D020820:Dyskinesias / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D020821:Dystonic Disorders / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D005190:Family; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D007223:Infant; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010661:Phenylketonurias / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D006136:GTP Cyclohydrolase
keywords: Dopa-responsive dystonia; GTP cyclohydrolase I gene; Korean