Brain Phe Impact

Brain Phe Impact

Phenylketonuria (PKU) is a lifelong metabolic disorder that can cause serious neurological toxicity1,2

PKU results in elevations in phenylalanine (Phe), which can be disruptive to brain morphology and function.2-5

Reevaluate Phe levels and clinical manifestations to optimize treatment plans.6

Emerging evidence

The long-term effects of high or unstable Phe in early-treated PKU patients, particularly adults, is only beginning to be understood.3,5

New approaches to PKU management will be guided by an increased understanding of the relationship between the pathophysiological changes and clinical manifestations of PKU.6 is dedicated to supporting knowledge-sharing across specialties so that you can change the future of PKU.

High blood Phe levels can cause damage to the brain1,2

Neurological damage has been seen in patients with PKU. Studies show that high or unstable Phe levels are the primary factor associated with neurological damage.3,5

Researchers continue to characterize the consequences of high or unstable Phe on the brain. This evidence highlights the importance of lowering and maintaining Phe levels.2-4,6

The clinical manifestations of high or unstable Phe levels7,8

Clinical studies reaffirm the relationship between high or unstable blood Phe levels and a range of suboptimal outcomes, such as depression, anxiety, and executive dysfunction.7,8

Despite continuous management of PKU, patients may still experience harmful neurological changes leading to disturbing symptoms and cognitive decline. Blood Phe levels should be evaluated in patients of all ages to determine the optimal management approach.3,6,9,10

The American College of Medical Genetics and Genomics (ACMG) guidelines for the treatment of PKU recommend that all patients, including those with late or untreated PAH deficiency, may benefit from institution of therapy.6

Adult patients who have discontinued treatment can experience improvements in neuropsychological function if they restart therapy.6

You can change the future of PKU

Complete the form below so you can stay up to date on the latest in PKU research, receive access to clinical publications on PKU management, and for opportunities to connect with peers. 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 high or unstable blood Phe levels in PKU, pathophysiology of PKU, and support tools.


  1. 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.
  2. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010;376(9750):1417-1427. doi:10.1016/S0140-6736(10)60961-0.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Cleary MA. Phenylketonuria. Paediatr Child Health. 2014;25(3):108-112. doi:10.1016/j.paed.2014.10.006.