Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood
IntroductionPhenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that disrupts neurotransmitter balance. Although early intervention has improved outcomes, neurocognitive challenges persist, particularly during adolescence. Metabolic control guidelines for patients aged >...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2025.1488809/full |
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| author | Beatriz Câmara Cristina Florindo Cláudia Bandeira de Lima Nélia Correia Inês Fernandes Manuela Batista Ana Gaspar Patrícia Janeiro Patrícia Janeiro |
| author_facet | Beatriz Câmara Cristina Florindo Cláudia Bandeira de Lima Nélia Correia Inês Fernandes Manuela Batista Ana Gaspar Patrícia Janeiro Patrícia Janeiro |
| author_sort | Beatriz Câmara |
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| description | IntroductionPhenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that disrupts neurotransmitter balance. Although early intervention has improved outcomes, neurocognitive challenges persist, particularly during adolescence. Metabolic control guidelines for patients aged >12 years differ between the European Union and the United States, with recommended blood Phe levels below 600 µM and 360 µM, respectively.MethodsThis study evaluated the relationship between blood Phe levels, intelligence quotient (IQ), and executive functions using the Wechsler Intelligence Scale for Children-Third Edition and the d2 Test of Attention. Blood Phe levels were monitored longitudinally and summarized using the Index of Dietary Control (IDC), calculated as the mean of individual annual median Phe concentrations, both before and after 12 years of age.ResultsThe study included 14 early-treated PKU patients aged 12–17 years, all diagnosed through newborn screening programs. Participants maintained good metabolic control (IDC <360 µM) prior to 12 years of age, with a mean IDC of 302 µM. Higher IQ scores before the age of 12 years were observed only among patients with consistent dietary compliance. After that age, attentional performance declined in those who were noncompliant with dietary recommendations. Additionally, occasional elevations in blood Phe levels at the time of cognitive assessments were associated with poorer cognitive performance.DiscussionThese findings underscore the detrimental effects of elevated Phe levels on executive functions during adolescence and highlight the need for larger studies to determine whether blood Phe levels between 360 and 600 µM are safe for patients aged >12 years. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pediatrics |
| spelling | doaj-art-35e70877d8c140a4bf33a91ec10f5ff42025-08-20T03:30:43ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-06-011310.3389/fped.2025.14888091488809Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhoodBeatriz Câmara0Cristina Florindo1Cláudia Bandeira de Lima2Nélia Correia3Inês Fernandes4Manuela Batista5Ana Gaspar6Patrícia Janeiro7Patrícia Janeiro8Pediatric Department, Funchal Central Hospital, SESARAM-EPERAM, Funchal, PortugalLaboratory of Metabolism and Genetics, Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, PortugalChild Development Center, Pediatric Department, Santa Maria’s Hospital-Lisbon North University Hospital Center, EPE, Pediatric University Clinic, Faculty of Medicine, University of Lisbon, Lisbon, PortugalChild Development Center, Pediatric Department, Santa Maria’s Hospital-Lisbon North University Hospital Center, EPE, Pediatric University Clinic, Faculty of Medicine, University of Lisbon, Lisbon, PortugalChild Development Center, Pediatric Department, Santa Maria’s Hospital-Lisbon North University Hospital Center, EPE, Pediatric University Clinic, Faculty of Medicine, University of Lisbon, Lisbon, PortugalChild Development Center, Pediatric Department, Santa Maria’s Hospital-Lisbon North University Hospital Center, EPE, Pediatric University Clinic, Faculty of Medicine, University of Lisbon, Lisbon, PortugalLisbon Reference Center for Metabolic Diseases, Department of Pediatrics, Hospital Santa Maria, Unidade Local de Saúde Santa Maria, Lisbon, PortugalLisbon Reference Center for Metabolic Diseases, Department of Pediatrics, Hospital Santa Maria, Unidade Local de Saúde Santa Maria, Lisbon, PortugalFaculdade de Medicina, Universidade de Lisboa, Lisbon, PortugalIntroductionPhenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that disrupts neurotransmitter balance. Although early intervention has improved outcomes, neurocognitive challenges persist, particularly during adolescence. Metabolic control guidelines for patients aged >12 years differ between the European Union and the United States, with recommended blood Phe levels below 600 µM and 360 µM, respectively.MethodsThis study evaluated the relationship between blood Phe levels, intelligence quotient (IQ), and executive functions using the Wechsler Intelligence Scale for Children-Third Edition and the d2 Test of Attention. Blood Phe levels were monitored longitudinally and summarized using the Index of Dietary Control (IDC), calculated as the mean of individual annual median Phe concentrations, both before and after 12 years of age.ResultsThe study included 14 early-treated PKU patients aged 12–17 years, all diagnosed through newborn screening programs. Participants maintained good metabolic control (IDC <360 µM) prior to 12 years of age, with a mean IDC of 302 µM. Higher IQ scores before the age of 12 years were observed only among patients with consistent dietary compliance. After that age, attentional performance declined in those who were noncompliant with dietary recommendations. Additionally, occasional elevations in blood Phe levels at the time of cognitive assessments were associated with poorer cognitive performance.DiscussionThese findings underscore the detrimental effects of elevated Phe levels on executive functions during adolescence and highlight the need for larger studies to determine whether blood Phe levels between 360 and 600 µM are safe for patients aged >12 years.https://www.frontiersin.org/articles/10.3389/fped.2025.1488809/fulladolescent developmentcognitionexecutive functionintelligence testsphenylketonuria |
| spellingShingle | Beatriz Câmara Cristina Florindo Cláudia Bandeira de Lima Nélia Correia Inês Fernandes Manuela Batista Ana Gaspar Patrícia Janeiro Patrícia Janeiro Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood Frontiers in Pediatrics adolescent development cognition executive function intelligence tests phenylketonuria |
| title | Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood |
| title_full | Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood |
| title_fullStr | Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood |
| title_full_unstemmed | Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood |
| title_short | Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood |
| title_sort | rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood |
| topic | adolescent development cognition executive function intelligence tests phenylketonuria |
| url | https://www.frontiersin.org/articles/10.3389/fped.2025.1488809/full |
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