Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Clinical Nutrition

Protein substitutes for phenylketonuria in Europe: access and nutritional composition

Abstract

Background/Objectives:

Protein substitutes (PS) are an essential component in the dietary management of phenylketonuria (PKU). PS are available as phenylalanine-free amino-acid mixtures (AAM), glycomacropeptide-based PS (GMP) and large neutral amino acids (LNAA). There is a lack of information regarding their availability in different countries and comparison of their nutritional composition is limited. The objectives of this study were to identify the number of PS available in different European countries and Turkey and to compare their nutritional composition.

Subjects/Methods:

Members of the European Nutritionist Expert Panel on PKU (ENEP) (Portugal, Spain, Belgium, Italy, Germany, Netherlands, United Kingdom, Denmark and Turkey) provided data on PS available in each country. The nutritional composition of PS available in Portugal was analyzed.

Results:

The number of PS available in each country varied from 30 (Turkey) to 105 (Germany), with a median of 64. GMP was available only in Portugal, whereas LNAA was an option in Portugal, Italy, Turkey and Denmark. Some PS were designed for weaning. Many PS did not contain added fat and fiber. GMP contained the highest carbohydrate (CHO) and energy content as well as higher LNAA content compared with AAM. Only one AAM contained added fructo-oligosaccharides and galacto-oligosaccharides. AAM designed for the first year of life had the highest CHO, fat and LNAA contribution. Liquid AAM had lower CHO and fat contents compared with powdered AAM, but contained higher LNAA.

Conclusions:

There was widely dissimilar numbers of PS available in different countries. Nutritional composition of different PS was variable and should be considered before prescription.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1

References

  1. Camp KM, Parisi MA, Acosta PB, Berry GT, Bilder DA, Blau N et al. Phenylketonuria Scientific Review Conference: state of the science and future research needs. Mol Genet Metab 2014; 112: 87–122.

    CAS  Article  PubMed  Google Scholar 

  2. MacDonald A . Diet and compliance in phenylketonuria. Eur J Pediatr 2000; 159 (Suppl 2), S136–S141.

    CAS  Article  PubMed  Google Scholar 

  3. Yi SH, Singh RH . Protein substitute for children and adults with phenylketonuria. Cochrane Database Syst Rev 2008 (4), CD004731.

  4. Blau N, MacDonald A, van Spronsen F . There is no doubt that the early identification of PKU and prompt and continuous intervention prevents mental retardation in most patients. Mol Genet Metab 2011; 104 (Suppl), S1.

    CAS  Article  PubMed  Google Scholar 

  5. Rocha JC, van Spronsen FJ, Almeida MF, Ramos E, Guimaraes JT, Borges N . Early dietary treated patients with phenylketonuria can achieve normal growth and body composition. Mol Genet Metab 2013; 110 (Suppl), S40–S43.

    CAS  Article  PubMed  Google Scholar 

  6. Dokoupil K, Gokmen-Ozel H, Lammardo AM, Motzfeldt K, Robert M, Rocha JC et al. Optimising growth in phenylketonuria: current state of the clinical evidence base. Clin Nutr 2012; 31: 16–21.

    Article  PubMed  Google Scholar 

  7. Rocha JC, Martins MJ . Oxidative stress in phenylketonuria: future directions. J Inherit Metab Dis 2012; 35: 381–398.

    CAS  Article  PubMed  Google Scholar 

  8. Enns GM, Koch R, Brumm V, Blakely E, Suter R, Jurecki E . Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab 2010; 101: 99–109.

    CAS  Article  PubMed  Google Scholar 

  9. Robert M, Rocha JC, van Rijn M, Ahring K, Belanger-Quintana A, MacDonald A et al. Micronutrient status in phenylketonuria. Mol Genet Metab 2013; 110 (Suppl), S6–S17.

    CAS  Article  PubMed  Google Scholar 

  10. Stolen LH, Lilje R, Jorgensen JV, Bliksrud YT, Almaas R . High dietary folic acid and high plasma folate in children and adults with phenylketonuria. JIMD Rep 2014; 13: 83–90.

    Article  PubMed  Google Scholar 

  11. Evans S, Daly A, MacDonald J, Preece MA, Santra S, Vijay S et al. The micronutrient status of patients with phenylketonuria on dietary treatment: an ongoing challenge. Ann Nutr Metab 2014; 65: 42–48.

    CAS  Article  PubMed  Google Scholar 

  12. Aguiar A, Ahring K, Almeida MF, Assoun M, Belanger Quintana A, Bigot S et al. Practices in prescribing protein substitutes for PKU in Europe: no uniformity of approach. Mol Genet Metab 2015; 115: 17–22.

    CAS  Article  PubMed  Google Scholar 

  13. Pietz J, Kreis R, Rupp A, Mayatepek E, Rating D, Boesch C et al. Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. J Clin Invest 1999; 103: 1169–1178.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Strisciuglio P, Concolino D . New strategies for the treatment of phenylketonuria (PKU). Metabolites 2014; 4: 1007–1017.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Matalon R, Michals-Matalon K, Bhatia G, Burlina AB, Burlina AP, Braga C et al. Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine. J Inherit Metab Dis 2007; 30: 153–158.

    CAS  Article  PubMed  Google Scholar 

  16. Schindeler S, Ghosh-Jerath S, Thompson S, Rocca A, Joy P, Kemp A et al. The effects of large neutral amino acid supplements in PKU: an MRS and neuropsychological study. Mol Genet Metab 2007; 91: 48–54.

    CAS  Article  PubMed  Google Scholar 

  17. Ney DM, Blank RD, Hansen KE . Advances in the nutritional and pharmacological management of phenylketonuria. Curr Opin Clin Nutr Metab Care 2014; 17: 61–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Ney DM, Hull AK, van Calcar SC, Liu X, Etzel MR . Dietary glycomacropeptide supports growth and reduces the concentrations of phenylalanine in plasma and brain in a murine model of phenylketonuria. J Nutr 2008; 138: 316–322.

    CAS  Article  PubMed  Google Scholar 

  19. van Calcar SC, MacLeod EL, Gleason ST, Etzel MR, Clayton MK, Wolff JA et al. Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids. Am J Clin Nutr 2009; 89: 1068–1077.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Rocha JC, MacDonald A, Trefz F . Is overweight an issue in phenylketonuria? Mol Genet Metab 2013; 110 (Suppl), S18–S24.

    CAS  Article  PubMed  Google Scholar 

  21. European Commission. Foods for Special Medical Purposes. Available at: http://ec.europa.eu/food/food/labellingnutrition/medical/index_en.htm (last accessed 10th November 2014).

  22. MacDonald A, Evans S, Cochrane B, Wildgoose J . Weaning infants with phenylketonuria: a review. J Hum Nutr Diet 2012; 25: 103–110.

    CAS  Article  PubMed  Google Scholar 

  23. Hagedorn TS, van Berkel P, Hammerschmidt G, Lhotakova M, Saludes RP . Requirements for a minimum standard of care for phenylketonuria: the patients' perspective. Orphanet J Rare Dis 2013; 8: 191.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Blau N, Belanger-Quintana A, Demirkol M, Feillet F, Giovannini M, MacDonald A et al. Management of phenylketonuria in Europe: survey results from 19 countries. Mol Genet Metab 2010; 99: 109–115.

    CAS  Article  PubMed  Google Scholar 

  25. van Spronsen FJ, Ahring KK, Gizewska M . PKU—What is daily practice in various centres in Europe? Data from a questionnaire by the scientific advisory committee of the European Society of Phenylketonuria and Allied Disorders. J Inherit Metab Dis 2009; 32: 58–64.

    CAS  Article  PubMed  Google Scholar 

  26. Koletzko B, Beyer J, Brands B, Demmelmair H, Grote V, Haile G et al. Early influences of nutrition on postnatal growth. Nestle Nutr Inst Workshop Ser 2013; 71: 11–27.

    PubMed  Google Scholar 

  27. MacDonald A, Cochrane B, Wopereis H, Loveridge N . Specific prebiotics in a formula for infants with phenylketonuria. Mol Genet Metab 2011; 104 (Suppl), S55–S59.

    CAS  Article  PubMed  Google Scholar 

  28. Koletzko B, Brands B, Chourdakis M, Cramer S, Grote V, Hellmuth C et al. The Power of Programming and the EarlyNutrition Project: opportunities for health promotion by nutrition during the first thousand days of life and beyond. Ann Nutr Metab 2014; 64: 187–196.

    CAS  Article  PubMed  Google Scholar 

  29. MacDonald A, Lilburn M, Davies P, Evans S, Daly A, Hall SK et al. 'Ready to drink' protein substitute is easier is for people with phenylketonuria. J Inherit Metab Dis 2006; 29: 526–531.

    CAS  Article  PubMed  Google Scholar 

  30. Gokmen-Ozel H, MacDonald A, Daly A, Hall K, Ryder L, Chakrapani A . Long-term efficacy of 'ready-to-drink' protein substitute in phenylketonuria. J Hum Nutr Diet 2009; 22: 422–427.

    CAS  Article  PubMed  Google Scholar 

  31. MacDonald A, Ahring K, Dokoupil K, Gokmen-Ozel H, Lammardo AM, Motzfeldt K et al. Adjusting diet with sapropterin in phenylketonuria: what factors should be considered? Br J Nutr 2011; 106: 175–182.

    CAS  Article  PubMed  Google Scholar 

  32. Rocha JC, Martel F . Large neutral amino acids supplementation in phenylketonuric patients. J Inherit Metab Dis 2009; 32: 472–480.

    CAS  Article  PubMed  Google Scholar 

  33. van Spronsen FJ, de Groot MJ, Hoeksma M, Reijngoud DJ, van Rijn M . Large neutral amino acids in the treatment of PKU: from theory to practice. J Inherit Metab Dis 2010; 33: 671–676.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Ahring KK . Large neutral amino acids in daily practice. J Inherit Metab Dis 2010; 33 (Suppl 3), S187–S190.

    Article  PubMed  Google Scholar 

  35. Humphrey M, Truby H, Boneh A . New ways of defining protein and energy relationships in inborn errors of metabolism. Mol Genet Metab 2014; 112: 247–258.

    CAS  Article  PubMed  Google Scholar 

  36. Kaiser L, Allen LH . Position of the American Dietetic Association: nutrition and lifestyle for a healthy pregnancy outcome. J Am Diet Assoc 2008; 108: 553–561.

    CAS  Article  PubMed  Google Scholar 

  37. Lammardo AM, Robert M, Rocha JC, van Rijn M, Ahring K, Belanger-Quintana A et al. Main issues in micronutrient supplementation in phenylketonuria. Mol Genet Metab 2013; 110 (Suppl), S1–S5.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J C Rocha.

Ethics declarations

Competing interests

All authors have received compensation from Merck Serono as members of the European Nutritionist Expert Panel in PKU. AM has received research funding and honoraria from Nutricia, Vitaflo International, Arla, Sobi and Merck Serono. She is a member of the European Nutrition Expert Panel (Merck Serono international), a member of Sapropterin Advisory Board (Merck Serono international) and a member of the Advisory Board ELEMENT (Danone-Nutricia). MJP and MFdA declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pena, M., de Almeida, M., van Dam, E. et al. Protein substitutes for phenylketonuria in Europe: access and nutritional composition. Eur J Clin Nutr 70, 785–789 (2016). https://doi.org/10.1038/ejcn.2016.54

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2016.54

Further reading

Search

Quick links