Molecular Genetics and Metabolism

Use of tetrahydrobiopterin for treatment of patients with phenylketonuria (PKU) is a ‘‘hot topic” among patients and doctors taking care of them. An increasing number of publications are describing decreases in blood phenylalanine (Phe) concentrations in persons receiving tetrahydrobiopterin. From the practical point of view, however, data on the extent of tetrahydrobiopterin responsiveness are not always precise. In many cases only a proportional decrease in blood Phe is reported, corresponding to a given mutation of the phenylalanine hydroxylase (PAH) gene, whereas data on initial blood Phe concentration, concurrent dietary Phe intake, or actual increase in PAH activity after tetrahydrobiopterin load are not complete. On the other hand data on in vitro PAH activity observed in the presence of various mutations of the PAH gene are available [1–3] as well as a model of blood Phe kinetics in patients with PKU [4]. Therefore, using the above data, we tried to establish a method for calculating absolute PAH activity in newborns with PKU after tetrahydrobiopterin loading. We adapted the equation describing blood Phe kinetics [4]. We considered lower PAH activity observed in newborns (90% of the activity in adults) [5] and assumed Phe transamination activity in newborns at the level of 90% of that observed in adults. We considered also the higher amount of body water in newborns (approximately 75% of body mass) as well as the typical basic Phe requirement (Phe tolerance) in newborns with PKU and null activity of PAH (20 mg/kg/day as observed in our 1-month-old patients) and individual protein intake in children. The resulting equation (see below) was used for analysis of absolute PAH activity.