Literature Review: PKU

 

 

Phenylketonuria, also known as PKU, is an inherited disorder that can be detected in a routine newborn screening. It is an inborn error of phenylalanine metabolism where the enzyme phenylalanine hydroxylase that turns phenylalanine into tyrosine is deficient.1 This causes a significant buildup of phenylalanine in the blood and brain which has the potential to cause intellectual disabilities, epilepsy, and behavior problems.3  The most common clinical feature of untreated PKU and poor compliance is varying levels of intellectual disabilities depending on the period of time that poor compliance is sustained.4  Additionally, nutritional deficiencies are likely to occur such as vitamin D and B12 deficenecies.4 For individuals with this condition, they are required to have diets low in phenylalanine strictly followed for the entirety of their lives. There is no way to reverse or correct this condition.

The detection of PKU is done as part of a routine screening test via a blood test, usually a heel prick, in newborn babies within 48 hours of birth.2 The occurrence of PKU varies throughout the world, but on average it occurs in about 1 in every 10,000 babies.2 Most of the time treatment starts early because of the routine testing that occurs in infants. However, in those that have not gone through the blood screening and are living with PKU, it manifests itself in a few different ways. In older children, behavior symptoms such as self-harm or large tempers can be a reason to just get checked just in case.4 Additionally, skin issues are also prevalent symptoms of PKU. Fairer skin than normal, eczema, repeatedly being sick, tremors, epilepsy, tremors.5

Eating a diet low in phenylalanine is the main way that this condition is managed. Being that phenylalanine is an amino acid, avoiding protein or only consuming small, measurable, and manageable amounts of protein is required to prevent a buildup of phenylalanine in the blood and cause further damage within the body and brain. Varying foods contain different levels of phenylalanine. Animal proteins carry about 50mg of phenylalanine for every 1 gram, about 5% of every animal protein.1 Fruits and vegetables also contain some levels of phenylalanine, but at a much lower amount, about 20-40mg for every 1 gram.1 It is often not intuitive for individuals to think of plan sources as protein, but in the case of PKU, it is essential that this is considered and taken into account while managing a PKU condition. Additionally, there has been a development of formulary that is phenylalanine free but provides an additional variety of other amino acids.5 Another important measure to take during diet interventions is to take into consideration the additive, aspartame. Aspartame is a sweetener that should also be avoided and looked out for because it is converted to phenylalanine upon metabolism within the body.3 Some medicines, foods with sugar substitutes or labeled sugar-free, diet drinks, gum, etc. all should be looked at carefully to determine if there is aspartame content that needs to be accounted for in an PKU patient.3 An important consideration to be made is the basic need for protein in an individual with PKU. Often individuals with PKU will either be meeting their DRI’s for protein needs or will not be.6 Patients with PKU must strictly limit their intake of foods rich in protein, such as meats, fish, eggs, and dairy products.5 Low-protein high-starch natural foods such as potatoes, some vegetables (such as peas) can be eaten but only in restricted amounts.5

Dietitians play a key role in patients with PKU in all stages of life to ensure, through varying means such as a food frequency questionnaire, that patients are still receiving proper nutrition throughout their life with the added stress of needing to follow a diet.6 Patients with PKU will have varying tolerance levels to PKU.1 As such, the targeted blood phenylalanine concentrations should be within the range of 120-360 for pediatrics under age 12, and 120-600 for individuals over the age of 12.1 Managing this range is very individualized and should be monitored by the physician and dietitian. There has been additional research determining if there are supplemental measures that can be taken to improve the health of patients with PKU. Specific nutrient combinations (SNC) that have been determined to likely improve brain function have also been used for those follow a low phenylalanine diet.3 This has only been done in rodents at this point to determine brain cognitive behaviors.3 Promising results have been concluded, but the research has a long way to go.

 

 

References

 

  1. MacDonald A, van Wegberg AMJ, Ahring K, et al. PKU dietary handbook to accompany PKU guidelines [published correction appears in Orphanet J Rare Dis. 2020 Sep 1;15(1):230]. Orphanet J Rare Dis. 2020;15(1):171. Published 2020 Jun 30. doi:10.1186/s13023-020-01391-y
  2. van Spronsen FJ, Blau N, Harding C, Burlina A, Longo N, Bosch AM. Phenylketonuria. Nat Rev Dis Primers. 2021;7(1):36. Published 2021 May 20. doi:10.1038/s41572-021-00267-0
  3. van Wegberg AMJ, MacDonald A, Ahring K, et al. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017;12(1):162. Published 2017 Oct 12. doi:10.1186/s13023-017-0685-2
  4. Al Hafid N, Christodoulou J. Phenylketonuria: a review of current and future treatments. Transl Pediatr. 2015;4(4):304-317. doi:10.3978/j.issn.2224-4336.2015.10.07
  5. phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017;12(1):162. Published 2017 Oct 12. doi:10.1186/s13023-017-0685-2
  6. Mol Genet Metab Rep. 2021;28:100771. Published 2021 May 25. doi:10.1016/j.ymgmr.2021.100771

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