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Early initiation of L-dopa
therapy enables stable development of executive function in
tetrahydrobiopterin (BH4) deficiency.
Tanaka Y,
Kato M, Muramatsu
T, Saito F,
Sato S, Matsuo N,
Shintaku H, Okano
Y, Kondo H,
Nukazawa T.
Department of Paediatrics, Tokyo
Dental College, Ichikawa General Hospital, Chiba, Japan.
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.
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