Tetrahydrobiopterin in dystonia

Abstract

The pteridine cofactor of tyrosine and tryptophan hydroxylases, tetrahydrobiopterin (BH4), is concentrated in the striatum and other sites of brain monoamine synthesis and is a regulatory factor in the rate-limiting step of catecholamine synthesis. CSF content was decreased in eight patients with dystonic disorders (mean, 13.0 +/- 0.8 pmol/ml CSF compared with 20.6 +/- 1.4 in age-matched normals). We gave several trials of synthetic BH4 intravenously to 10 dystonic patients with benefit for 2 subjects with diurnally fluctuating dystonia, 1 with hemidystonia and parkinsonism, and 1 with generalized torsion dystonia. The findings of biopterin abnormality and the observed clinical improvements may point to a role for the cofactor in the pathogenesis and, possibly, the treatment of some forms of primary dystonia.