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Age-related psychophysiological vulnerability to phenylalanine in phenylketonuria
Vincenzo Leuzzi1, Daniela Mannarelli2, Filippo Manti1
1Department of Paediatrics, Child Neurology and Psychiatry, Sapienza Università di Roma , Rome , Italy.
Insights
Phenylketonuria (PKU) affects neurocognitive skills in adolescents. Rapid phenylalanine increases negatively impact event-related potentials and cognitive functions, especially in younger patients, highlighting the need for strict metabolic control.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Developmental Psychology
Background:
- Phenylketonuria (PKU) results from a phenylalanine hydroxylase enzyme defect, impacting phenylalanine (Phe) to tyrosine (Tyr) conversion.
- Early treatment of PKU has improved outcomes, but neurocognitive and psychiatric issues persist in adulthood.
- Understanding Phe's impact on complex skills is crucial for managing PKU's long-term effects.
Purpose of the Study:
- To investigate the effect of acute phenylalanine loading on event-related potentials (ERPs) in adolescents with PKU.
- To explore the relationship between psychophysiological responses and neurocognitive performance in PKU patients.
- To assess the vulnerability of developing neurocognitive functions to elevated phenylalanine levels.
Main Methods:
- Seventeen early-treated PKU subjects (aged 10-20) underwent ERP recordings (mismatch negativity, P300, CNV, Auditory Evoked Potentials) before and after oral Phe loading.
- Neurocognitive assessments, historical and current blood Phe, Tyr, and Phe/Tyr ratios were statistically analyzed.
- Specific ERP components, including CNV amplitude and P3b latency, were measured.
Main Results:
- ERPs were generally detectable, but Phe loading negatively affected CNV amplitude, W2-CNV area, P3b latency, and motor reaction times in subjects under 13.
- Neurocognitive skills were more impaired in younger PKU patients, irrespective of psychophysiological vulnerability.
- No significant correlation was found between biochemical markers (Phe, Tyr, Phe/Tyr ratio) and neurocognitive or psychophysiological findings.
Conclusions:
- Emerging neurocognitive functions in adolescents with PKU are vulnerable to phenylalanine levels.
- Strict metabolic control is recommended for adolescents with PKU.
- A neurodevelopmental perspective is essential for studying neurocognitive outcomes in PKU.
Background:
Phenylketonuria (PKU) is caused by the inherited defect of the phenylalanine hydroxylase enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). Neonatal screening programs and early treatment have radically changed the natural history of PKU. Nevertheless, an increased risk of neurocognitive and psychiatric problems in adulthood remains a challenging aspect of the disease. In order to assess the vulnerability of complex skills to Phe, we explored: (a) the effect of a rapid increase in blood Phe levels on event-related potentials (ERP) in PKU subjects during their second decade of life; (b) the association (if existing) between psychophysiological and neurocognitive features.
Methods:
Seventeen early-treated PKU subjects, aged 10-20, underwent ERP [mismatch negativity, auditory P300, contingent negative variation (CNV), and Intensity Dependence of Auditory Evoked Potentials] recording before and 2 h after an oral loading of Phe. Neurocognitive functioning, historical and concurrent biochemical values of blood Phe, Tyr, and Phe/Tyr ratio, were all included in the statistical analysis.
Results:
Event-related potential components were normally detected in all the subjects. In subjects younger than 13 CNV amplitude, W2-CNV area, P3b latency, and reaction times in motor responses were negatively influenced by Phe-loading. Independently from the psychophysiological vulnerability, some neurocognitive skills were more impaired in younger patients. No correlation was found between biochemical alterations and neurocognitive and psychophysiological findings.
Conclusion:
The vulnerability of the emerging neurocognitive functions to Phe suggests a strict metabolic control in adolescents affected by PKU and a neurodevelopmental approach in the study of neurocognitive outcome in PKU.
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