Modelling the phenylalanine blood level response during treatment of phenylketonuria.

A vast body of phenylketonuria (PKU) patient monitoring data is deposited in clinical files and, after having served the actual needs, has remained there largely unused. We propose a kinetic model that will allow continued analysis of such data for further elucidation of the patient's metabolic phenotype and phenylalanine (Phe) disposal characteristics. Our PKU model of a single compartment with the input of alimentary Phe and two outputs--(1) first-order Phe conversion to tyrosine and acidic metabolites, and (2) zero-order Phe usage for net protein synthesis--has been developed with the graphics-oriented ModelMaker (then Cherwell Scientific Ltd, Oxford, UK) software package. The corresponding differential and integrated rate equations are presented to enable transfer of the model to equation-oriented simulation packages. The model offers a possible explanation for discrepancies in some genotype-phenotype data.