Dynamics of hyperphenylalaninemia and intellectual outcome in teenagers with phenylketonuria

  • Bożena Didycz Department of Medical Genetics, Jagiellonian University Medical College
  • Miroslaw Bik-Multanowski Department of Medical Genetics, Faculty of Medicine, Jagiellonian University Medical College
Keywords: Inborn error of metabolism, metabolic control of PKU, treatment adherence


Insufficient treatment adherence after early childhood is frequently observed in patients with phenylketonuria. Assessment of these individuals’ long-term metabolic control could enable early detection of the risk of intellectual deterioration related to hyperphenylalaninemia. However, the predictive value of specific parameters of phenylalanine dynamics is not clear.

Here, we assessed the impact of blood phenylalanine fluctuations during the first 12 years of life on cognitive outcome in early and continuously treated teenagers with phenylketonuria.

We analyzed a total of 5141 results of blood phenylalanine measurements in 32 patients. The phenylalanine levels of these patients during early childhood were usually acceptable, but the control of hyperphenylalaninemia worsened and the average treatment adherence dropped to 40% during late primary school.

Our analysis revealed strong associations between Wechsler intelligence test verbal scores and the mean of yearly means of phenylalanine concentrations (r= -0.62). The correlations of IQ scores with median phenylalanine concentrations and the variability of blood phenylalanine levels were weaker. Wechsler verbal scores were also strongly correlated with treatment adherence level during preschool and late primary school (r= 0.61 and 0.72).

The mean of yearly means of blood phenylalanine concentrations appears to be a better predictor of cognitive outcome in children with phenylketonuria than other parameters related to phenylalanine dynamics. The percentage of acceptable phenylalanine levels below 50–60% should be regarded as a “red light” due to the risk of intellectual deterioration in patients.


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