European Journal of Pediatrics

, Volume 144, Issue 1, pp 13–16 | Cite as

Atypical phenylketonuria with “dihydrobiopterin synthetase” deficiency: Absence of phosphate-eliminating enzyme activity demonstrated in liver

  • A. Niederwieser
  • W. Leimbacher
  • H. Ch. Curtius
  • A. Ponzone
  • F. Rey
  • D. Leupold
Original Investigations


An assay for the phosphate-eliminating enzyme (PEE) activity in liver was developed which required only 5–10 mg tissue. PEE catalyses the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin (BH4). In the presence of substrate, magnesium, NADPH, and a sepiapterin reductase fraction from human liver, PEE catalysed the formation of BH4 which was measured by HPLC and electrochemical detection. In adult human liver, a PEE activity of 1.02±0.134 μU/mg protein (mean ±1 SD; n=5) was observed. In liver needle biopsy material from five patients with defective biopterin biosynthesis, no PEE activity was found (less than 2% and 6% of the control values, respectively). The presence of an endogenous inhibitor was excluded. In a patient who died without definite diagnosis and in a patient with β-thalassaemia liver PEE activity was increased. Sepiapterin reductase activity was present in all cases. Results indicate that in “dihydrobiopterin synthetase” deficiency, the most frequent of the rare BH4-deficient variants of hyperphenylalaninaemia, the molecular defect consists in a defect of PEE.

Key words

Phenylketonuria Biopterin Dihydrobiopterin Inborn errors of metabolism 



Phosphate eliminating enzyme


Dihydrobiopterin synthetase


High pressure liquid chromatography




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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • A. Niederwieser
    • 1
  • W. Leimbacher
    • 1
  • H. Ch. Curtius
    • 1
  • A. Ponzone
    • 2
  • F. Rey
    • 3
  • D. Leupold
    • 4
  1. 1.Department of PediatricsUniversity of ZurichZurichSwitzerland
  2. 2.Department of PediatricsUniversity of TorinoItaly
  3. 3.Hopital des Enfants-MaladesUniversity of ParisFrance
  4. 4.Department of PediatricsUniversity of UlmFederal Republic of Germany

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