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The lifelong impact of PKU is
underrecognized1-3

People with PKU can experience higher rates of serious neuropsychiatric symptoms4-6

Estimated prevalence ratios of diagnoses for patients with PKU compared with the general population

*P<0.05.
Abbreviations: ADD, attention deficit disorder; ADHD, attention deficit hyperactivity disorder.
Adapted from Bilder et al. Mol Genet Metab. 2017.

The effects of high Phe are felt throughout a patient’s life1

  • Controlling Phe levels in newborns and children prevents permanent intellectual disability1,6
  • However, adolescents and adults with uncontrolled Phe can experience neurologic, psychiatric, and cognitive symptoms, including:6

Executive Function is Thought to be Particularly Affected7

Executive function is a collection of cognitive skills required to self-regulate and organize mental efforts in order to achieve goals8

Processing Speed7

Comprehension, ability to complete tasks, and school or work performance

Working Memory9

Ability to hold information in mind that will be used to guide one’s actions; whether now or at a later point in time

Attention9

Ability to sustain attention or persistence of effort with tasks

Impulse Control8,9

Self-regulation, such as control to avoid “off-limit” foods and refrain from outbursts or challenging behavior (critical for fulfilling responsibilities of adulthood)

Planning and Organization8

Thinking out acts and purposes in advance; examples include meal planning, task planning, and thought organization

Mental and emotional stress of PKU10

Even patients with blood Phe ≤500 μmol/L in childhood showed a higher frequency of psychiatric diagnoses, such as:

Effects Of PKU

Patients and their caregivers struggle with PKU symptoms11

When you can cause irreversible brain damage to your child, it causes a lot of worry, stress, and even panic.11

Parent

I have blank moments where I can’t think or get my words out that I am trying to say. I experience anxiety and I get paranoid.11

Patient with PKU

I get “brain fog”, tend to become irritable and uneasy in social settings.11

Patient with PKU

The burden of PKU extends beyond the brain and into many aspects of adult life12

Adults with PKU have an increased risk of several multisystemic comorbidities

 

Prevalence ratio graph

Adapted from Burton et al. Mol Genet Metab. 2018.

Patients with PKU struggle to maintain safe blood Phe levels13,14

  • A Phe-restricted diet is burdensome and can provide inadequate protein intake unless supplemented with medical nutrition therapy1,15
  • Phe control typically drops off during adolescence1,13
  • By adulthood, most patients in the United States have Phe levels exceeding guideline recommendations13,14
Play

Connie: Learning to Focus on Herself
See how returning to clinic afer 50 years helped Connie achieve the best Phe levels of her life.

View transcript

Learn more about PKU

Learn more about elevated Phe and symptoms

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Learn more about dietary control with PKU

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Know your PKU management options

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References: 1. Vockley J, Andersson HC, Antshel KM, et al. American College of Medical Genetics and Genomics Therapeutic Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guidelines. Genet Med. 2014;16(2):188-200. 2. ten Hoedt AE, de Sonneville LMJ, Francois B, et al. High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial. J Inherit Metab Dis. 2011;34(1):165-171. 3. Trefz KF, Muntau AC, Kohlscheen KM, et al. Clinical burden of illness in patients with phenylketonuria (PKU) and associated comorbidities―a retrospective study of German health insurance claims data. Orphanet J Rare Dis. 2019;14(1):181. doi:10.1186/s13023-019-1153-y. 4. Ashe K, Kelso W, Farrand S, et al. Psychiatric and cognitive aspects of phenylketonuria: the limitations of diet and promise of new treatments. Front Psychiatry. 2019;10:561. doi:10.3389/fpsyt.2019.00561. 5. Bilder DA, Kobori JA, Cohen-Pfeffer JL, Johnson EM, Jurecki ER, Grant ML. Neuropsychiatric comorbidities in adults with phenylketonuria: a retrospective cohort study. Mol Genet Metab. 2017;12(1):1-8. 6. van Wegberg AMJ, MacDonald A, Ahring K, et al. The complete European guidelines of phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017;12(1):162. doi: 10.1186/s13023-017-0685-2. 7. Bone A, Kuehl A, Angelino A. A neuropsychiatric perspective of phenylketonuria I; overview of phenylketonuria and its neuropsychiatric sequelae. Psychosomatics. 2012;53(6):517–523. 8. Bilder DA, et al. Systematic review and meta-analysis of neuropsychiatric symptoms and executive functioning in adults with phenylketonuria. Dev Neuropsychol. 2016;41(4):245-260. 9. Diamond A. Executive functions. Annu Rev Psychol. 2013;64:135-168. 10. Manti F, Nardecchia F, Chiarotti F, Carducci C, Leuzzi V. Psychiatric disorders in adolescent and young adult patients with phenylketonuria. Mol Genet Metab. 2016;117(1):12-18. 11. Ford S, O’Driscoll M, MacDonald A. Living with phenylketonuria: lessons from the PKU community. Mol Genet Metab Rep. 2018;17:57-63. 12. Burton BK, Jones KB, Cederbaum S, et al. Prevalence of comorbid conditions among adult patients diagnosed with phenylketonuria. Mol Genet Metab. 2018;125(3):228-234. 13. Brown CS, Lichter-Konecki U. Phenylketonuria (PKU): a problem solved? Mol Genet Metab Rep. 2016;6:8-12. 14. Jurecki ER, Cederbaum S, Kopesky J, et al. Adherence to clinic recommendations among patients with phenylketonuria in the United States. Mol Genet Metab. 2017;120(3):190-197. 15. van Spronsen FJ, van Wegberg AMJ, Ahring K, et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol. 2017;5(9):743-756.