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Kinetic study of catecholamine metabolism in hereditary progressive dystonia.

Kinetics of catecholamine biosynthesis and metabolism have been examined in patients with hereditary progressive dystonia with marked diurnal fluctuation of symptoms (HPD, Segawa's disease). Three patients and a healthy control received an oral load of deuterated tyrosine, and monodeuterium labelled catecholamines and their metabolites in urine and plasma were examined by gas chromatography-mass spectrometry. Patients excreted normal amounts of the primary metabolites of dopamine (dihydroxyphenylacetic acid, homovanillic acid) in urine, suggesting normal rates of dopamine production. However, the biological half-life of dopamine in the patients was reduced to about half that of controls. Noradrenaline biosynthesis and metabolism were normal. Taken together, these results are interpreted to show a reduced biological half-life of dopamine in the brains of these patients, possibly caused by a defect in dopamine storage. Impaired dopamine storage may be the basis of the diurnal fluctuation in symptoms.