title: Genetics and biochemistry of dopa-responsive dystonia: significance of striatal tyrosine hydroxylase protein loss.
abstract: Notwithstanding the discovery of GCH1 and TH mutations in autosomal-dominant and autosomal-recessive DRD, respectively, a therapeutic trial with levodopa is still the most practical approach to the diagnosis of DRD. The trial needs to be considered in all children with dystonic and/or parkinsonian symptoms or with unexplained gait disorders. Further accumulation of patients with TH-deficient DRD (the mild form of TH deficiency) is necessary to establish the clinical characteristics of this disorder. Regarding GTPCH-deficient DRD, there remain important unresolved issues, including questions of incomplete penetrance of GCH1 mutations, female predominance of affected subjects, and intrafamilial phenotypic variation. A clarification of the mechanism of striatal TH protein loss in GTPCH-deficient DRD may provide a new clue to the pathogenesis of this major form of DRD.
authors.affiliation: Movement Disorders Research Laboratory, Centre for Addiction and Mental Health-Clarke Division, Toronto, Ontario, Canada.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001708:Biopterins / Q000172:deficiency / Q000235:genetics; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis / Q000172:deficiency*; D020821:Dystonic Disorders / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D006136:GTP Cyclohydrolase / Q000172:deficiency / Q000235:genetics; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics*; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency*
chemical_list: D001708:Biopterins; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase; D004298:Dopamine; D006719:Homovanillic Acid