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.
Furukawa
Yoshiaki
Y
Movement Disorders Research Laboratory, Centre for Addiction and Mental Health-Clarke Division, Toronto, Ontario, Canada. yoshiaki_furukawa@camh.net
Kapatos
Gregory
G
Haycock
John W
JW
Worsley
Julian
J
Wong
Henry
H
Kish
Stephen J
SJ
Nygaard
Torbjoern G
TG
D000978:Antiparkinson Agents / Q000627:therapeutic use; D001708:Biopterins / Q000235:genetics*; D001921:Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004421:Dystonia / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008875:Middle Aged; D013577:Syndrome; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D000978:Antiparkinson Agents; D001708:Biopterins; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase