Brain GTP cyclohydrolase I protein reduction in dopa-responsive dystonia: a clue to the pathogenesis.

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Many patients with dopa-responsive dystonia (DRD) have shown mutations in the gene encoding GTP cyclohydrolase I (GTPCH). However, there have been no reports of GTPCH protein levels in the brain of human subjects and the actual status of striatal GTPCH in DRD is unknown. We measured GTPCH protein concentrations for the first time in the autopsied human brain and found the following; 1) the expression level of this protein was high in the striatum, 2) concentrations of GTPCH protein in the putamen were substantially decreased in patients with GTPCH-deficient DRD (-76% [mean]) and were significantly reduced in patients with Parkinson disease (-53%), and 3) GTPCH protein levels in the putamen increased in early postnatal period (1-28 days), reached a plateau in childhood, and decreased in adulthood (17-99 years).