Adult Phenylketonuria Challenges

  • Alan FungMedical Biotechnology and Business Management – MSc, University of Warwick, Coventry

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Overview

Phenylketonuria (PKU) is a genetic disorder characterised by a build-up of phenylalanine, one of the 20 amino acids humans need to create proteins. Phenylalanine is typically broken down by the enzyme phenylalanine hydroxylase (PAH), but functional copies of PAH are not present in people with PKU.1 The resultant build-up of phenylalanine is the cause of the symptoms associated with PKU.

Individuals with PKU from different age groups display different symptoms. Infants have growth problems, most noticeably a smaller-than-average head (known as microcephaly), eczema and heart issues. These symptoms carry into adulthood, but others can arise, such as damage to the brain and nervous system that causes learning difficulties. The skin and urine may also have an unpleasant smell.

Conditions caused by PKU extend into lifetime challenges for adults, some based on symptoms, others more so regarding treatment feasibility, pregnancy or social settings. As PKU is inherited and has the potential to cause significant symptoms, this condition does not have a cure. However, measures in response to these symptoms can manage PKU effectively.

Adherence to dietary restrictions

Phenylalanine is considered an essential amino acid, a building block of proteins that the human body cannot produce.2 These amino acids must therefore be obtained from food as part of a balanced diet; however, high-protein foods should be avoided since they raise phenylalanine levels even more in PKU patients. High-protein foods to avoid include:

  • Meat and fish
  • Soya
  • Mushrooms
  • Nuts and seeds

While an adjustment, this is considered the most straightforward measure you can take to limit phenylalanine intake.

Collectively, the tendency for someone to stick to any form of treatment is referred to as adherence, and this can be low both unintentionally (from accidental consumption) or intentionally (due to lack of self-control) for PKU sufferers who need to eat low-phenylalanine diets.2

Although a single instance of eating one of the above foods is unlikely to cause you significant harm, it is important to keep protein levels as low as possible to keep PKU symptoms to a minimum. Adherence can be reinforced via diet journaling, goal-setting or seeking assistance from a dietician.

Interviews of adults with PKU revealed that some find it not only difficult to avoid phenylalanine completely, but when blood-phenylalanine levels increase it makes it harder to rectify; this has the potential to lead to a vicious cycle.

Difficulties with exercise

The aorta is the largest artery we have, which transports oxygenated blood from the heart to other parts of the body. PKU can lead to coarctation of the aorta, causing restricted blood flow and subsequently less oxygen reaching muscles.3 This can make exercises difficult due to fatigue.

Due to reduced protein intake, it is likely to be more difficult to build muscle through strenuous exercises such as weight lifting or callisthenics than if you do not have PKU. Daily light exercise is encouraged, with at least 30 to 45 minutes dedicated to it being recommended for most people.

Exercise itself does not reduce phenylalanine levels; this must come from diet and/or necessary medication.

Oxygen consumption in PKU patients

A study has shown positive effects of exercise on breathing capacity in PKU patients. These patients were provided with a low-phenylalanine diet with a metabolic formula to ensure other amino acids were obtained.4

Alongside a control group of healthy individuals, PKU patients were categorised as either “well controlled” or “poorly controlled” based on being below or over 700 μmol/L of phenylalanine concentration in the blood.

Figure 1: Comparisons of VO2 peak readings in comparison to healthy individuals without PKU. Readings were taken 30 minutes after light aerobic exercise. There were 16 people in the control, 5 people in the well-controlled group and 3 people in the poorly-controlled group. Error bars indicate standard deviation. CTL = control, PKU = phenylketonuria.4

These patients carried out 30 minutes of light aerobic exercise (treadmill jogging), and their rate of oxygen consumption (VO2) peak readings were noted during exercise. In turn, this corresponded with the biggest breath patients took while exercising. No participants from either of the three groups did any exercise before the experiments commenced.

In comparison to the control, the poorly controlled group had a significantly lower VO2 peak, whereas it was similar for the well-controlled group. [Fig. 1] This data suggests that dietary adherence is crucial to optimising your capabilities for exercise, thus improving overall health, regardless of problems such as aortic coarctation.

Monitoring of conditions

The concentration of phenylalanine in the blood is the easiest and most reliable indicator of your health if you have PKU. While it is easy to measure blood glucose levels at home (such as for diabetics), blood extraction and analysis must be done at a clinic or hospital by doctors or nurses. This is usually only done once a month, but it is important not to skip these tests to ensure monitoring is consistent. General practitioners (GPs) should be able to access your hospital records, including blood-phenylalanine levels, providing advice and guidance from there.

As high-protein diets are not recommended for people with PKU, you may be asked to keep food records if your GP requests you to. Some people may find this approach more useful than others, but it is a good way of helping identify foods to avoid should your phenylalanine blood levels increase unexpectedly.

Home testing kits for blood-phenylalanine

Handheld home testing kits have been in development in the United States; however, these are unlikely to be commercially available soon, let alone here in the UK.

A cheaper alternative to designing a new product was evaluated, using a blood sample (such as via finger prick) and an ammonia detection system. An enzyme called phenylalanine ammonia-lyase (PAL) reacts with phenylalanine to produce ammonia, which in turn can be measured by the detector; the more phenylalanine present in the blood, the more ammonia that is produced.5

Due to the small size of the blood sample, the amount of ammonia produced is not harmful. As PAL is an enzyme, it can be reused for the next time you want to gauge your blood-phenylalanine levels, but it typically works better if it has been freeze-dried prior to use. The enzymatic activity of PAL decreases with subsequent use, so eventually, you will need to replace it to ensure results are accurate.

The ammonia reader is portable and handheld and easily accessible to buy online. Together, these advantages can allow you to monitor your PKU at any time you want and more frequently than current procedures that widespread healthcare offers.

This is, however, yet to be finalised into a singular product that can be inspected for safety and effectiveness before people with PKU can benefit. The issue of PAL “expiring” also needs to be addressed before this testing kit can be considered viable.

Neurobehavioural problems

Due to brain damage that can occur as early as birth, different psychiatric and mental problems can occur:

  • Mood instability
  • Attention deficits and hyperactivity (ADHD may be present and diagnosed)6
  • Learning difficulties

Such problems are commonly viewed as significant in growing up (i.e., during childhood and adolescence), notably in a school setting, but these can affect adults in daily life also. This includes depression, panic attacks and irrational fears (also known as phobias).

Even with diet monitoring and restriction, the neurological effects of PKU may still impact your life; however, their severity is affected by your phenylalanine levels. Some adults may experience self-loathing at the idea of having a disorder such as PKU, which further affects mood and self-esteem.7

Phenylalanine is a precursor molecule that eventually is converted into dopamine, the neurotransmitter associated with the “reward system” in the brain. While no evidence has been found yet, this is believed to be behind the neurological traits in people with PKU.8

The effects on mood and mental health can be related directly to PKU itself, for example, being frustrated at dietary restrictions or more outward, such as lack of motivation to complete tasks and general anxiety about work life. Adults also claim that they have been unable to enter romantic relationships and even friendships due to an aversion to social settings altogether.9 It is not uncommon for adults with PKU to live with their parents/family and to be unmarried.

Summary

There is no feasible way to give PAH to people with PKU, but there are different approaches available to minimise symptoms caused by the phenylalanine build-up. The most common of these is to avoid foods containing phenylalanine; however, the neurobehavioural effects of this condition make this challenging, ranging from anxiety due to societal pressure to depression due to hormone imbalance.

Research has shown that if you have PKU, you are able to lead a relatively normal and healthy life; however, these benefits must come from self-control in dietary restriction. On top of this, monitoring blood-phenylalanine levels can be seen as inconvenient, having to be carried out at a clinic or hospital and once a month. Home testing kits are yet to be available to the public, regardless of the great potential they appear to have.

Overall, it is possible for someone with PKU to have a high quality of life as if they do not have this condition; however, there are several factors that prevent this solution from being straightforward. If you struggle with PKU, listen to the advice your doctor or GP provides you with, and talk to a professional if you are struggling with your mental health.

References

  1. Phenylketonuria - an overview | ScienceDirect Topics [Internet]. [cited 2024 Apr 19]. Available from: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/phenylketonuria 
  2. Phenylalanine - an overview | ScienceDirect Topics [Internet]. [cited 2024 Apr 19]. Available from: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/phenylalanine
  3. Levy HL, Guldberg P, Güttler F, Hanley WB, Matalon R, Rouse BM, et al. Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. Pediatr Res. 2001; 49(5):636–42
  4. Mazzola PN, Teixeira BC, Schirmbeck GH, Reischak-Oliveira A, Derks TGJ, Spronsen FJ van, et al. Acute exercise in treated phenylketonuria patients: Physical activity and biochemical response. Mol Genet Metab Rep [Internet]. 2015 [cited 2024 Apr 19]; 5:55–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471389/ 
  5. Wada Y, Totsune E, Mikami-Saito Y, Kikuchi A, Miyata T, Kure S. A method for phenylalanine self-monitoring using phenylalanine ammonia-lyase and a pre-existing portable ammonia detection system. Mol Genet Metab Rep [Internet]. 2023 [cited 2024 Apr 19]; 35:100970. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068251/
  6. BECKHAUSER MT, BEGHINI MENDES VIEIRA M, MOEHLECKE ISER B, ROZONE DE LUCA G, RODRIGUES MASRUHA M, LIN J, et al. Attention Deficit Disorder with Hyperactivity Symptoms in Early-Treated Phenylketonuria Patients. Iran J Child Neurol [Internet]. 2020 [cited 2024 Apr 19]; 14(1):93–103. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956970/.
  7. Targum SD, Lang W. Neurobehavioral Problems Associated with Phenylketonuria. Psychiatry (Edgmont) [Internet]. 2010 [cited 2024 Apr 19]; 7(12):29–32. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028461/
  8. Simon E, Schwarz M, Roos J, Dragano N, Geraedts M, Siegrist J, et al. Evaluation of quality of life and description of the sociodemographic state in adolescent and young adult patients with phenylketonuria (PKU). Health Qual Life Outcomes [Internet]. 2008 [cited 2024 Apr 19]; 6:25. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2329607/
  9. Ford S, O’Driscoll M, MacDonald A. Living with Phenylketonuria: Lessons from the PKU community. Mol Genet Metab Rep [Internet]. 2018 [cited 2024 Apr 19]; 17:57–63. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198120/

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Alan Fung

Medical Biotechnology and Business Management – MSc, University of Warwick, Coventry

Alan is a Healthcare Article Writer and Freelance Content Writer, having several months of experience within the health communications field. He has years of experience in literature review via his university education as well as science communication through a variety of media such as posters, presentations and essays. Alan has a robust and ever-growing portfolio of science content ranging from the unknown benefits of different fruits to the different treatment strategies in place for genetic disorders.

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