ArticleOrphanet journal of rare diseases2019
Adult cognitive outcomes in phenylketonuria: explaining causes of variability beyond average Phe levels.
Article in Orphanet journal of rare diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Italian national consensus statement on management and pharmacological treatment of phenylketonuria.Orphanet journal of rare diseases · 2021Pooled it
- Effects of a Prolonged-Release Protein Substitute on 24-h Phenylalanine and Tyrosine Profiles in Phenylketonuria: A Randomized Crossover Study.Nutrients · 2026Trial
- Randomized investigation to evaluate phenylalanine fluctuation after overnight fasting in PKU patients treated with prolonged-release versus standard amino acid protein substitute.Orphanet journal of rare diseases · 2026Trial
- Lower blood phenylalanine concentrations may be of clinical benefit in adults with phenylketonuria.Molecular genetics and metabolism reports · 2026Article
- Navigating adulthood with PKU: metabolic outcomes, quality of life, and mental health 4.5 years post-transition.Orphanet journal of rare diseases · 2026Article
- Review
- The influence of professionals' personal views and values in the development of guidelines for rare diseases: an example from phenylketonuria.Orphanet journal of rare diseases · 2025Article
- Executive Functions and Long-Term Metabolic Control in Adults with Phenylketonuria (PKU).Metabolites · 2025Article
- Phenylketonuria as an Adherence Disease.Patient preference and adherence · 2025Review
- Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons.Molecular genetics and metabolism reports · 2024Article
- Extensive Dysregulation of Phenylalanine Metabolism Is Associated With Stress Hyperphenylalaninemia and 30-Day Death in Critically Ill Patients With Acute Decompensated Heart Failure.Journal of the American Heart Association · 2024Article
- Blood Phenylalanine Levels in Patients with Phenylketonuria from Europe between 2012 and 2018: Is It a Changing Landscape?Nutrients · 2024Article
- Efficient in vivo prime editing corrects the most frequent phenylketonuria variant, associated with high unmet medical need.American journal of human genetics · 2023Article
- Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria.Nutrients · 2023Article
- Total choline intake and working memory performance in adults with phenylketonuria.Orphanet journal of rare diseases · 2023Article
- Cognitive Functioning in Adults with Phenylketonuria in a Cohort of Spanish Patients.Behavioural neurology · 2023Article
- Characterization of Choline Nutriture among Adults and Children with Phenylketonuria.Nutrients · 2022Article
- Serum glial fibrillary acidic protein and neurofilament light chain in patients with early treated phenylketonuria.Frontiers in neurology · 2022Article
- Observational
- Phenylketonuria.Nature reviews. Disease primers · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe objective was to deepen the understanding of the causes of individual variability in phenylketonuria (PKU) by investigating which metabolic variables are most important for predicting cognitive outcomes (Phe average vs Phe variation) and by assessing the risk of cognitive impairment associated with adopting a more relaxed approach to the diet than is currently recommended.
methodWe analysed associations between metabolic and cognitive measures in a mixed sample of English and Italian early-treated adults with PKU (N = 56). Metabolic measures were collected through childhood, adolescence and adulthood; cognitive measures were collected in adulthood. Metabolic measures included average Phe levels (average of median values for each year in a given period) and average Phe variations (average yearly standard deviations). Cognition was measured with IQ and a battery of cognitive tasks.
resultsPhe variation was as important, if not more important, than Phe average in predicting adult outcomes and contributed independently. Phe variation was particularly detrimental in childhood. Together, childhood Phe variation and adult Phe average predicted around 40% of the variation in cognitive scores. Poor cognitive scores (> 1 SD from controls) occurred almost exclusively in individuals with poor metabolic control and the risk of poor scores was about 30% higher in individuals with Phe values exceeding recommended thresholds.
conclusionsOur results provide support for current European guidelines (average Phe value = < 360 μmol/l in childhood; = < 600 μmo/l from 12 years onwards), but they suggest an additional recommendation to maintain stable levels (possibly Phe SD = < 180 μmol/l throughout life). PUBLIC SIGNIFICANCE STATEMENTS: We investigated the relationship between how well people with phenylketonuria control blood Phe throughout their life and their ability to carry out cognitive tasks in adulthood. We found that avoiding blood Phe peaks was as important if not more important that maintaining average low Phe levels. This was particularly essential in childhood. We also found that blood Phe levels above recommended European guidelines was associated with around 30% increase in the risk of poor cognitive outcomes.
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