GTP cyclohydrolase I gene, dystonia, juvenile parkinsonism, and Parkinson's disease.
GTP cyclohydrolase I is the rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin, which is the cofactor for tyrosine hydroxylase, the rate-limiting enzyme for dopamine biosynthesis. We found that dominantly inherited, hereditary progressive dystonia (HPD), first described by Segawa and also called dopa responsive dystonia (DRD), is caused by the mutations of GTP cyclohydrolase I gene, the partial decrease in the enzyme activity, and probably in striatal dopamine level, to less than 20% of the normal values. Juvenile parkinsonism and Parkinson's disease are also striatal dopamine deficiency, but no mutation in the enzyme has not been found, and they are supposed to be different from HPD/DRD in which no cell death of the nigrostriatal dopamine neurons occurs.
Nagatsu
T
T
Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Ichinose
H
H
D000328:Adult; D017668:Age of Onset; D000818:Animals; D003342:Corpus Striatum / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D004421:Dystonia / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D006136:GTP Cyclohydrolase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D017354:Point Mutation
D006136:GTP Cyclohydrolase; D004298:Dopamine