A four year old girl presented with Parkinsonian symptoms suggestive of cerebral dopamine deficiency - profound hypokinesia, bradykinesia, tremor of the limbs and tongue, an expressionless face, drooling and trunkal hypotonia. Brain MRI and EEG were normal. No clinical improvement on therapy with L-DOPA, CSF concentrations of homovanillic acid, reflecting the overall flow through the dopamine pathway was not reduced but highly increased instead with 2050 nmol/l (normal 400-650). Its precursor, 3,4-dihydroxyphenylacetic acid was also found elevated at 22 nmol/l (normal < 5). CSF concentrations of phenylalanine, tyrosine, L-DOPA, 3-ortho-methyl-Dopa, vanillactic acid, 3-methoxytyramine, 3-methoxy-4-hydroxyphenylethyleneglycol, 5-hydroxytryptophane, and 5-hydroxyindoleacetic acid were all normal.

This pattern of neurotransmitter metabolites has hitherto not been reported. It excludes the known defects in dopamine biosynthesis and is suggestive of a primary defect of dopamine receptors or postreceptor signalling pathways. BZM SPECT scan of the child showed a substantial decreased labelling of D2 receptors in the basal ganglia (K. Joseph, klin. Nuklearmedizin, Marburg, Germany). We believe that this may represent the first documented case of a defect of dopamine D2 receptors in humans. Molecular analysis is in progress.