Journal of Inherited Metabolic Disease

, Volume 32, Issue 1, pp 40–45

Effect of BH4 supplementation on phenylalanine tolerance

BH4 and PKU

DOI: 10.1007/s10545-008-0947-1

Cite this article as:
Burlina, A. & Blau, N. J Inherit Metab Dis (2009) 32: 40. doi:10.1007/s10545-008-0947-1



Tetrahydrobiopterin (BH4) is a potential new orphan drug for the treatment of some patients with phenylketonuria (PKU), mostly mild forms. Numerous studies have confirmed this finding and BH4-responsiveness may be predicted to some extent from the corresponding genotype.


To investigate the response to BH4 loading test, the phenylalanine hydroxylase (PAH) mutations and the long-term therapeutic efficacy of BH4 in patients with PKU, and to better define BH4-responsive patients according to phenylalanine (Phe) levels and dietary phenylalanine tolerance.


30 Italian PKU patients (age range: 6 months–24 years; 12 female, 18 male) were included in this retrospective study. Eleven out of 30 patients presented with Phe levels below 450 μmol/L and 19 patients with Phe levels between 450 and 900 μmol/L. In the second group, we investigated the effect of long-term (6 months–7 years) oral administration of BH4 on blood Phe levels and daily Phe tolerance.


In all patients with initial blood Phe levels <450 μmol/L (n = 11), BH4 loading test was positive, but no treatment was introduced. In 12 out of 19 patients with blood Phe levels >450 μmol/L and positive at BH4 loading, the treatment with BH4 (10 mg/kg per day) was initiated. Before BH4 treatment, Phe tolerance was less than 700 mg/day in all patients except for one (patient no. 9), increasing to 2–3-fold (from 498 ± 49 to 1475 ± 155 mg/day) on BH4 treatment. In these patients the amino acid mixture supplementation was stopped and the diet was a combination of low-protein foods and natural proteins, mostly from animal sources.


Long-term BH4 substitution (up to 7 years) in a group of moderate PKU patients allowed a substantial relaxation of the dietary restrictions or even replacement of the diet with BH4 without any adverse effects.









phenylalanine hydroxylase





Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Division of Metabolic Diseases, Department of PediatricsUniversity HospitalPaduaItaly
  2. 2.Division of Clinical Chemistry and BiochemistryUniversity Children’s HospitalZürichSwitzerland
  3. 3.Metabolic Unit, Department of PediatricsUniversity HospitalPadovaItaly

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