Brain biopterin and tyrosine hydroxylase in asymptomatic dopa-responsive dystonia

It is assumed that brain biopterin and dopamine loss should not be as severe in asymptomatic dopa-responsive dystonia caused by GCH1 mutations as it is in symptomatic dopa-responsive dystonia. However, the actual status of dopaminergic systems in asymptomatic cases is unknown. In the autopsied putamen of an asymptomatic GCH1 mutation carrier, we found that brain biopterin loss (-82%) paralleled that reported in dopa-responsive dystonia patients (-84%). However, tyrosine hydroxylase protein and dopamine levels (-52 and -44%, respectively) were not as severely affected as in symptomatic patients (exceeding -97 and -88%, respectively). Our data suggest that the extent of striatal tyrosine hydroxylase protein loss may be critical in determining dopa-responsive dystonia symptomatology.