Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin

Mol Genet Metab. 2005 Dec:86 Suppl 1:S75-80. doi: 10.1016/j.ymgme.2005.06.026. Epub 2005 Oct 20.


Tetrahydrobiopterin (BH4), the natural cofactor of phenylalanine hydroxylase (EC, can reduce blood phenylalanine (Phe) in BH4 sensitive patients with hyperphenylalaninemia (McKuisick 261600). We report on the long-term treatment of eight patients with mild and classical phenylketonuria (blood Phe levels maximum blood Phe levels between 771 and 1500 micromol/L) using BH4 at a dosage of 8-12 mg/kg BW per day. In all patients reduction of blood Phe was >30% after BH4 loading test. Three patients were treated from birth by BH4 only, five after initial low Phe dietary treatment. Seven of them continue to be on BH4 treatment only, one has a relaxed low protein diet. No side effects could be observed (longest observation time 5 years), somatic and psychomotor development were normal. The main problem of BH4 treatment is finding an optimal dosage at different ages and an under special conditions like infectious diseases. There is evidence that in some patients BH4 treatment may allow a more relaxed low protein diet showing positive effects on weight gain and quality of life. Further controlled studies are necessary not only to rule out any side effects but also for optimizing treatment strategies with BH4 treatment in mild phenylketonuria.

MeSH terms

  • Biopterins / administration & dosage
  • Biopterins / analogs & derivatives*
  • Biopterins / therapeutic use
  • Combined Modality Therapy
  • Diet, Protein-Restricted
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Phenylalanine / blood
  • Phenylalanine Hydroxylase / genetics
  • Phenylketonurias / blood
  • Phenylketonurias / diet therapy
  • Phenylketonurias / drug therapy*
  • Weight Gain


  • Biopterins
  • Phenylalanine
  • Phenylalanine Hydroxylase
  • sapropterin