Possible effects of tetrahydrobiopterin treatment in six children with autism--clinical and positron emission tomography data: a pilot study.

Six children, between 3 and 5 years of age, having infantile autism according to DSM-III-R, were treated for 3 months with 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-BH4), a cofactor for tyrosine hydroxylases in the biosynthetic pathway of catecholamines and serotonin. A criterion for inclusion in the study was a relatively low level of R-BH4 in the cerebrospinal fluid. For clinical evaluation, the Parental Satisfaction Survey (PASS) was used every fourth week and the Griffiths Developmental Scales were used before starting and 3 months after completing the treatment. During the treatment period, all parents reported improvements in the child's social functioning-mainly eye contact and desire to interact-and in the number of words or sounds which the child used. Small positive changes were noted on the Griffiths Developmental Scales between the two testing occasions. R-BH4 levels in CSF increased significantly after treatment. The positron emission tomography (PET) study showed that the high value of dopamine D2 receptor binding in the caudate and putamen decreased by about 10% towards the normal level after treatment with R-BH4. The observations in this open study indicate that the drug might be useful for a subgroup of children with autism, but there is a need for a larger double-blind study with a longer treatment period.