Pilot study to evaluate the effects of tetrahydrobiopterin on adult individuals with phenylketonuria with measurable maladaptive behaviors.

OBJECTIVES

To evaluate the effects of tetrahydrobiopterin (BH4) on maladaptive behavior in patients with phenylketonuria (PKU).

METHODS

In an effort to determine if BH4 has any effects on the central nervous system, we studied 10 individuals with PKU and measurable maladaptive behaviors for 1 year. Behavioral assessments using the Vineland Adaptive Behavior Scales-Second Edition and a PKU Behavior Checklist were obtained at baseline, 6 months, and at the end of the study. Biochemical measures including plasma amino acids were obtained quarterly, and phenylalanine (Phe) and tyrosine (Tyr) were obtained monthly.

RESULTS

Out of the 10 subjects, 2 were responders to BH4, as determined by a blood Phe reduction >30%. While blood Phe in the 8 nonresponders did not change significantly throughout the study, their Tyr levels were significantly higher at 6 months (p=0.012), but not at 12 months (p=0.23). By the end of the study, 8 subjects exhibited fewer maladaptive behaviors on the components of the Vineland Maladaptive Behavior Index, and all 10 had lower total scores on the PKU Behavior Checklist.

CONCLUSION

These findings suggest that there may be direct effects of BH4 on the central nervous system, independent of lowering blood Phe.