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

Published online by Cambridge University Press:  17 October 2014

Kathryn D. Moseley ,
Martha J. Ottina ,
Colleen G. Azen  and
Shoji Yano
Kathryn D. Moseley*
Affiliation:
Genetics Division, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles County+University of Southern California Medical Center, Los Angeles, California, USA
Martha J. Ottina
Affiliation:
Genetics Division, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles County+University of Southern California Medical Center, Los Angeles, California, USA
Colleen G. Azen
Affiliation:
Clinical and Translational Science Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Shoji Yano
Affiliation:
Genetics Division, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles County+University of Southern California Medical Center, Los Angeles, California, USA
*
*Address for correspondence: Kathryn D. Moseley, M.S., R.D., Genetics Division, Department of Pediatrics, Keck School of Medicine, University of Southern California, LAC+USC Medical Center, 1801 Marengo St., Rm. 1G-24, Los Angeles, CA 90033, USA. (Email: kmoseley@usc.edu)
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Abstract

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.

Keywords

phenylalaninephenylketonuriatetrahydrobiopterintyrosine hydroxylase
Type
Original Research
Information
CNS Spectrums , Volume 20 , Issue 2 , April 2015 , pp. 157 - 163
Copyright
© Cambridge University Press 2014 

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Footnotes

The authors wish to thank Dr. Richard Koch, who was a key contributor to this study.

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