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Long-term follow-up of patients with phenylketonuria receiving tetrahydrobiopterin treatment

  • Research Report
  • Published:
Journal of Inherited Metabolic Disease


Treatment with tetrahydrobiopterin (BH4), the natural cofactor of phenylalanine hydroxylase (PAH), can reduce blood phenylalanine (Phe) levels in patients with BH4-responsive phenylketonuria (PKU). A number of studies has reported on the short-term BH4 treatment of patients with PKU, but long-term data are lacking. Here, we describe the effects of long-term treatment with BH4 on 16 patients, who showed a >28% reduction in blood Phe following testing for BH4 overload. The mean dose of BH4 was 16 mg/kg body weight (range 5–36 mg/kg body weight). The mean treatment duration was 56 months (range 24–110 months). Of 16 patients, 14 achieved long-term Phe control with BH4 treatment, with a mean blood Phe concentration of 321 ± 236 µmol/l. The mean decrease from baseline in blood Phe levels in these 14 patients was 54.6%. Of the seven patients who required continued dietary restriction, Phe intake increased from 200–300 mg/day to 800–1000 mg/day. Factors that may cause fluctuation of Phe levels in BH4-treated patients include patients’ PAH genotype, Phe intake, changes in protein catabolism or anabolism, and periods of illness or infection.

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BH4 :



Enzyme Commission


Hamburg Wechsler Intelligenz-Test für Kinder


mild hyperphenylalaninaemia


Online Mendelian Inheritance in Man database


phenylalanine hydroxylase






rare metabolic disease database


standard deviation


standard error of estimation


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The authors take full responsibility for the content of this article but thank Caudex Medical (supported by Serono Symposia International Foundation) for their assistance in preparing the initial draft of this report and collating the comments of the authors and any other named contributors.

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Correspondence to Friedrich K. Trefz.

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Communicated by: Nenad Blau

Reference to electronic databases: EC, OMIM, RAMEDIS

Competing interest: None declared.

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Trefz, F.K., Scheible, D. & Frauendienst-Egger, G. Long-term follow-up of patients with phenylketonuria receiving tetrahydrobiopterin treatment. J Inherit Metab Dis 33 (Suppl 3), 163–169 (2010).

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