Dopamine transporter density measured by [123I]β-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia

The clinical distinction between dopa‐responsive dystonia (DRD) and juvenile Parkinson's disease (JPD) can pose a diagnostic challenge. Both conditions are dopa responsive. However, long‐term L‐dopa benefit is very different between the two. The difference in the prognosis is due to presence or absence of nigral cell loss. In JPD, there is degenerative nigral cell loss, wherease there are enzymatic defects in dopamine synthesis without cell loss in DRD. Mutations have been found in the GTP cyclohydrolase I (GCH‐I) and tyrosine hydroxylase genes in DRD. As the discovered mutations are multiple and more are expected to be found, it is difficult to confirm or exclude DRD by mutation studies. Measurement of cerebrospinal fluid (CSF) neopterin will detect DRD from mutations in the GCH‐I gene but not from mutations in tyrosine hydroxylase. The dopamine transporter (DAT) is a protein in the dopaminergic nerve terminals. (1R)‐2β‐Carbomethoxy‐3β‐(4‐[123I]iodophenyl)tropane ([123I]β‐CIT) is a ligand for the DAT, and it was shown to be a useful nuclear imaging marker for neurons that degenerate in Parkinson's disease (PD). As DRD was shown to have a normal DAT without nigral cell loss in a postmortem study, we predicted that the DAT measured in vivo by nuclear imaging will be normal in DRD and will differentiate DRD from JPD. Therefore, we performed [123I]β‐CIT single‐photon emission computed tomography ([123I]β‐CIT SPECT) in clinically diagnosed DRD, PD, and JPD, and examined whether DAT imaging can differentiate DRD from PD and JPD. We then examined whether DAT imaging can provide a screening tool for molecular genetic studies, by studying mutations in the candidate gene GCH‐I and measuring CSF neopterin. Five females (4 from two families, and 1 sporadic) were diagnosed as DRD based on early‐onset foot dystonia and progressive parkinsonism beginnig at ages 7 to 12. All patients were functioning normally on L‐dopa 100 to 250 mg/day for up to 8 years. SPECT imaging was obtained after intravenous injection of [123I]β‐CIT; 15 healthy volunteers served as normal control, and 6 PD and 1 JPD as disease controls. [123I]β‐CIT striatal binding was normal in DRD, whereas it was markedly decreased in PD and JPD. Gene analysis showed a novel nonsense mutation in the GCH‐I gene in one family. No mutation was found in the other family or in the sporadic case. CSF neopterin was markedly decreased in the 4 tested patients. [123I]β‐CIT SPECT is a sensitive method for probing the int