title: A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene.
abstract: We report a case of a 46-year-old Japanese woman with hereditary progressive dystonia with marked diurnal fluctuations and dopa-responsive dystonia (HPD/DRD). She developed difficulty in walking at the age of 44 years due to bradykinesia as well as hand tremors, muscle rigidity, increased tendon reflexes and mild dystonia in the lower extremities, all of which responded remarkably to low doses of levodopa (150 mg/day). Biopterin and neopterin concentrations in the cerebrospinal fluid (CSF) were decreased. Analysis of the guanosine 5'-triphosphate cyclohydrolase I (GCH1) gene revealed a novel mutation (W53X) in one allele. The GCH1 activity that was expressed in mononuclear blood cells was almost half the normal value (usually 2-20% of the normal value (39.0+/-9.2 pmol/ml) in patients with HPD/DRD). The relatively conserved GCH1 activity that is expressed in stimulated peripheral blood mononuclear cells may be related to the late clinical symptoms in this patient.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. furuya@neuro.med.kyushu-u.ac.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Furuya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takasugi
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ohyagi
authors.forename: Fumi
authors.initials: F
authors.lastname: Urano
authors.forename: Taroh
authors.initials: T
authors.lastname: Kishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichinose
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D001708:Biopterins / Q000134:cerebrospinal fluid; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D015259:Dopamine Agents / Q000627:therapeutic use*; D020821:Dystonic Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006136:GTP Cyclohydrolase / Q000097:blood / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019798:Neopterin / Q000134:cerebrospinal fluid; D009460:Neurologic Examination; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D015259:Dopamine Agents; D001708:Biopterins; D007980:Levodopa; D019798:Neopterin; D006136:GTP Cyclohydrolase