Metabolic control and clinical outcome in adolescents with phenylketonuria

Agnese De Giorgi, Francesca Nardecchia, Cristina Romani, Vincenzo Leuzzi

Research output: Contribution to journalArticlepeer-review


The main neurological, cognitive, and behavioural consequences of phenylketonuria have been eradicated thanks to new-born screening and Phe-restricted diet therapy. However, the effects of high phenylalanine levels during adolescence and adulthood on neurocognitive functions remain a concern. This systematic review aimed at collecting clinical data suggesting the safest metabolic target for early treated PKU during the second decade of life. Twenty studies met the inclusion criteria for full-text review. Relevant studies included papers that (a) examined the relationship between metabolic control and neurocognitive functions during adolescence or (b) investigated the impact of metabolic control in adolescence on adult outcomes. Most studies showed a positive correlation between metabolic control during adolescence and neurocognitive outcomes across ages. This was true both for IQ and executive functions, although data on executive functions were less clear, and it remains to be established whether they are more vulnerable to Phe than IQ. Taken together present evidence confirm brain vulnerability to Phe during adolescence and suggests that low average Phe levels and low Phe fluctuations should be maintained throughout life. While results are fully compatible with current European recommendations, clinical and methodological limitations coupled with remarkable interindividual variability prevented a clear identification of a safe threshold for Phe blood levels during adolescence.

Original languageEnglish
Article number107684
JournalMolecular Genetics and Metabolism
Issue number3
Early online date12 Aug 2023
Publication statusPublished - 1 Nov 2023


  • Adolescence
  • Metabolic control
  • Executive function
  • Phenylketonuria
  • Outcome
  • Cognition


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