title: 6-Pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: a clinical and molecular study.
abstract: We report the case of a 44-year-old woman with a partial 6-pyruvoyl tetrahydropterin synthase (6-PTS) deficiency, whose predominant clinical symptom was generalized dystonia with marked diurnal fluctuation. Dystonia was present in the eyelids, oromandibular region, trunk, and extremities (Meige syndrome plus double hemiplegia-like dystonia). A marked and sustained positive response to levodopa was observed. A molecular genetic study revealed a homozygous mutation (I114V) in the 6-PTS gene. This study indicates that genetic abnormality in the 6-PTS gene may be a hereditary dystonia disorder. We speculate that our patient has residual 6-PTS activity in the central nervous system, such as in the liver, and we suggest that residual, but insufficient production of tetrahydrobiopterin may play an important role in causing diurnal fluctuation of symptoms.
authors.affiliation: Department of Psychiatry, Yokohama City University of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hanihara
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: C
authors.initials: C
authors.lastname: Kawanishi
authors.forename: N
authors.initials: N
authors.lastname: Sugiyama
authors.forename: T
authors.initials: T
authors.lastname: Miyakawa
authors.forename: H
authors.initials: H
authors.lastname: Onishi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Osaka
authors.forename: K
authors.initials: K
authors.lastname: Kosaka
authors.forename: K
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: M
authors.initials: M
authors.lastname: Owada
mesh_terms: D000328:Adult; D000429:Alcohol Oxidoreductases / Q000172:deficiency*; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001483:Base Sequence; D001545:Benserazide / Q000008:administration & dosage / Q000627:therapeutic use; D002940:Circadian Rhythm; D004359:Drug Therapy, Combination; D004421:Dystonia / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011622:Pterins / Q000652:urine
chemical_list: D000978:Antiparkinson Agents; D011622:Pterins; D007980:Levodopa; D001545:Benserazide; D000429:Alcohol Oxidoreductases; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase