Brain Phe Impact
Phenylketonuria (PKU) is a lifelong metabolic disorder with risk of serious neurological consequences1,2
PKU results in elevations in phenylalanine (Phe), which can be neurotoxic and disruptive to brain morphology and function.2-5
Reevaluate Phe levels and clinical manifestations to optimize treatment plans.6
While the significant and long-lasting damage caused by elevations in Phe continues to be explored in clinical studies,7,8 the delayed effects of these elevations and the consequences of long-term exposure are only beginning to be studied.3,5
Increasing our knowledge of the neurological effects of PKU—and their connection to clinical manifestations—may guide new approaches in management.6
PKUBrain.com is dedicated to supporting knowledge-sharing across specialties so that we can help change the future of PKU.
Elevations in Phe can cause damage to the brain1,2
Neurological damage has been seen in patients with PKU. Across studies, elevations in Phe have been identified as the primary cause.3,5
As researchers continue to identify the brain damage caused by elevations in Phe, understanding of the importance of lowering Phe levels increases, challenging existing Phe targets. 2-4,6
Elevations in Phe are connected to clinical manifestations8-10
In clinical studies, patients with PKU can exhibit a range of suboptimal outcomes associated with dysfunctions in the brain. These outcomes often correlate with variable and chronic elevations in blood Phe levels.8-10
Despite continuous management of their PKU, patients may still experience white matter damage and cognitive decline. Evaluate Phe levels and management approaches for patients of all ages to ensure optimal outcomes.3,6,11,12
Help change the future of PKU
Register now and we will contact you as the site is updated. Increasing our knowledge of the neurological effects of PKU—and their connection to clinical manifestations—may guide new approaches in management.6
We look forward to being a reliable source of information about the effects of elevations in Phe in PKU, approaches to management, and support tools.
- de Groot MJ, Hoeksma M, Blau N, Reijngoud DJ, van Spronsen FJ. Pathogenesis of cognitive dysfunction in phenylketonuria: review of hypotheses. Mol Genet Metab. 2010;99(suppl 1):S86-S89. doi:10.1016/j.ymgme.2009.10.016.
- Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010;376(9750):1417-1427. doi:10.1016/S0140-6736(10)60961-0.
- Mastrangelo M, Chiarotti F, Berillo L, et al. The outcome of white matter abnormalities in early treated phenylketonuric patients: a retrospective longitudinal long-term study. Mol Genet Metab. 2015;116(3):171-177. doi:10.1016/j.ymgme.2015.08.005.
- Christ SE, Price MH, Bodner KE, Saville C, Moffitt AJ, Peck D. Morphometric analysis of gray matter integrity in individuals with early-treated phenylketonuria. Mol Genet Metab. 2016;118(1):3-8. doi:10.1016/j.ymgme.2016.02.004.
- Waisbren SE, Noel K, Fahrbach K, et al. Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab. 2007;92(1-2):63-70. doi:10.1016/j.ymgme.2007.05.006.
- Vockley J, Andersson HC, Antshel KM, et al; for American College of Medical Genetics and Genomics Therapeutic Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188-190. doi:10.1038/gim.2013.157.
- Anastasoaie V, Kurzius L, Forbes P, Waisbren S. Stability of blood phenylalanine levels and IQ in children with phenylketonuria. Mol Genet Metab. 2008;95(1-2):17-20. doi:10.1016/j.ymgme.2008.06.014.
- Hood A, Grange DK, Christ SE, Steiner R, White DA. Variability in phenylalanine control predicts IQ and executive abilities in children with phenylketonuria. Mol Genet Metab. 2014;111(4):445-451. doi:10.1016/j.ymgme.2014.01.012.
- Pietz J, Fätkenheuer B, Burgard P, Armbruster M, Esser G, Schmidt H. Psychiatric disorders in adult patients with early-treated phenylketonuria. Pediatrics. 1997;99(3):345-350. doi:10.1542/peds.99.3.345
- Bilder DA, Noel JK, Baker ER, et al. Systematic review and meta-analysis of neuropsychiatric symptoms and executive functioning in adults with phenylketonuria [published online November 2, 2016]. Dev Neuropsychol. doi:10.1080/87565641.2016.1243109.
- Nardecchia F, Manti F, Chiarotti F, Carducci C, Carducci C, Leuzzi V. Neurocognitive and neuroimaging outcome of early treated young adult PKU patients: a longitudinal study. Mol Genet Metab. 2015;115(2-3):84-90. doi:10.1016/j.ymgme.2015.04.003.
- Cleary MA. Phenylketonuria. Paediatr Child Health. 2014;25(3):108-112. doi:10.1016/j.paed.2014.10.006.