ORAL PHENYLALANINE LOADING IN DOPA-RESPONSIVE DYSTONIA - A POSSIBLE DIAGNOSTIC-TEST

To determine if there is abnormal phenylalanine and biopterin metaboli sm in patients with dopa-responsive dystonia (DRD), we measured plasma levels of phenylalanine, tyrosine, biopterin, and neopterin at baseli ne, and 1, 2, 4, and 6 hours after an oral phenylalanine load (100 mg/ kg). Seven adults with DRD, two severely affected children with DRD, a nd nine adult controls were studied. AU patients had phenylalanine and tyrosine concentrations within the normal range at baseline. In the a dult patients, phenylalanine levels were higher than in controls at 2, 4, and 6 hours post-load (p < 0.0005); tyrosine concentrations were l ower than control levels at 1, 2, and 4 hours post-load(p < 0.05). Phe nylalanine to tyrosine ratios were elevated in patients at all times p ost-load (p < 0.0005). Biopterin levels in the patients were decreased at baseline and 1, 2, and 4 hours post-load (p < 0.005). Pretreatment with tetrahydrobiopterin (7.5 mg/kg) normalized phenylalanine and tyr osine profiles in two adult patients. In the children with DRD, phenyl alanine to tyrosine ratios were slightly elevated at baseline. Followi ng phenylalanine loading, the phenylalanine profiles were similar to t hose seen in the adult patients but there was no elevation in plasma t yrosine. Baseline biopterin levels were lower in the children with DRD than in the adult patients or the controls and there was no increase in biopterin post-load. In both the children and adults with DRD, neop terin concentrations did not differ from control values at baseline or after phenylalanine load. The results are consistent with decreased L iver phenylalanine hydroxylase activity due to defective synthesis of tetrahydrobiopterin in patients with DRD. The findings show that a phe nylalanine load may be useful in the diagnosis of this disorder.