Article Text

  1. M Bik-Multanowski1,
  2. J J Pietrzyk1,
  3. B Didycz1,
  4. A Szymczakiewicz-Multanowska1
  1. 1Department of Pediatrics, Jagiellonian University, Krakow, Poland


Tetrahydrobiopterin (BH4) increases phenylalanine hydroxylase (PAH) activity and can normalise the blood phenylalanine concentration in some patients with phenylketonuria. However, lack of precise methods for in-vivo PAH activity measurement makes the assessment of BH4 treatment effects only semi-quantitative.

The aim of the study was to establish a model for calculating absolute phenylalanine hydroxylase activity in newborns with phenylketonuria receiving BH4.

Methods: A mathematical equation for assessment of PAH activity in newborns was constructed with the use of previously published data on blood phenylalanine kinetics in adults (Kaufman, Proc Nat Acad Sci 1996;3160–4). Lower basic PAH activity and phenylalanine transamination activity, a higher amount of body water, dietary protein intake and phenylalanine tolerance in newborns with phenylketonuria were considered. The model was validated by means of a retrospective analysis of PAH activity in 10 newborns with phenylketonuria who received BH4.

Results: The equation ΔPhe/t  =  −0.9 k vPAH − 0.9 vTrans + Phefood was used for calculating PAH activity where ΔPhe/t is the blood phenylalanine increase rate, k is the PAH residual activity ratio, vPAH is the maximal phenylalanine hydroxylation rate in adults, vTrans is the phenylalanine transamination rate in adults, Phefood is the diet-related blood phenylalanine increase rate. The calculated in-vivo enzymatic activities correlated with published in-vitro data on PAH activities observed in the presence of mutations of the PAH gene. In three cases (patients heterozygous for BH4-responsive mutations) PAH activities higher than predicted were observed, which probably reflects BH4 responsiveness.

Conclusion: Our method allows for the estimation of absolute PAH activity in newborns with phenylketonuria and can be useful for measurement of the BH4 treatment effect.

Funding: Supported by government grant N40708032/3085.

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