title: Early initiation of L-dopa therapy enables stable development of executive function in tetrahydrobiopterin (BH4) deficiency.
abstract: Executive function (EF) has been presumed to be mediated by the dopaminergic system in the prefrontal cortex. However, little is known about the early development of this function and the roles dopamine plays in it. Tetrahydrobiopterin (BH4) deficiencies are genetic disorders affecting catecholamine and serotonin biosynthesis which, if untreated, result in motor and cognitive symptoms including impairment of EF. A comprehensive neuropsychological test battery was administered to six participants with BH4 deficiency (four males, two females, mean Full-scale intelligence quotient [FIQ] 63.8 [SD 14.7]); all were on replacement therapy with L-dopa and BH4, but time of initiation of treatment varied. Age range (median) was 28 days to 41 years (2y 6mo) at initiation of treatment and 10 to 47 years (19y) at follow-up. On non-EF tests, performance agreed with those of IQ-matched controls (four males, two females; mean age 16y 6mo [SD 6mo]; mean FIQ 62.3 [SD 13.4]). On EF tests those who initiated treatment after 2 years 6 months of age performed poorly. In patients with BH4 deficiency, replacement therapy should be started in the first weeks or months of life. Patients diagnosed before the age of 2 years 6 months obtain normal EF, which suggests dopamine may play a critical role in ensuring stable development of EF in early life.
authors.affiliation: Department of Paediatrics, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Motoichiro
authors.initials: M
authors.lastname: Kato
authors.forename: Taro
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Fumie
authors.initials: F
authors.lastname: Saito
authors.forename: Seiji
authors.initials: S
authors.lastname: Sato
authors.forename: Nobutake
authors.initials: N
authors.lastname: Matsuo
authors.forename: Haruo
authors.initials: H
authors.lastname: Shintaku
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Okano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Nukazawa
mesh_terms: D006916:5-Hydroxytryptophan / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000172:deficiency; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D019761:Phosphorus-Oxygen Lyases / Q000008:administration & dosage / Q000172:deficiency; D011340:Problem Solving / Q000187:drug effects*; D016896:Treatment Outcome; D014888:Wechsler Scales
chemical_list: D001708:Biopterins; D007980:Levodopa; D006916:5-Hydroxytryptophan; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin