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.

  • Original Article
  • Published:

Clinical Nutrition

Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source

European Journal of Clinical Nutrition volume 71, pages 1230–1234 (2017)Cite this article

Subjects

Abstract

Background/Objectives:

Low phenylalanine (PHE), glycomacropeptide-based protein substitute (GMP) is an alternative to traditional L-amino acid supplements (AA) used in the dietary management of phenylketonuria (PKU). In a retrospective, longitudinal study, we report the nutritional status of PKU patients taking AA and GMP.

Subjects/Methods:

Eleven PKU patients aged 27±10 years (1 HPA, 4 mild and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body composition, blood pressure measurements, biochemical markers including vitamin, mineral, lipids, carbohydrates and protein status/metabolism, and nutritional intake assessment) at two different annual reviews. The mean time taking AA was 13±5 months and GMP 13±7 months. Blood phenylalanine (PHE) and tyrosine (TYR) were analysed before and after GMP introduction.

Results:

Both GMP and AA protein substitutes provided similar protein equivalent intake (0.85 vs 0.75 g/kg/day, P=0.182). In the GMP group, it contributed 57% (27–100%) of the protein substitute intake (with AA delivering the rest of protein substitute intake), providing an additional 34±12 mg/day PHE. Nutritional intake, anthropometry and body composition measurements were similar in both the groups. Median blood PHE did not change (P=0.594), although values within target range improved (36 vs 46%), but this was not statistically significant. Mean blood TYR increased (52.0±19.2 vs 63.2±25.6 μmol/l, P=0.033), and all biochemical markers remained stable, except for a lower A1C haemoglobin (P=0.011).

Conclusions:

Partial GMP contribution to total protein substitute intake did not affect nutritional status in patients with PKU. Blood PHE control was not adversely affected. The increased blood TYR after GMP introduction necessitates further study.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Blau N, van Spronsen FJ, Levy HL . Phenylketonuria. Lancet 2010; 376: 1417–1427.

    Article  CAS  Google Scholar 

  2. MacDonald A, Rocha JC, van Rijn M, Feillet F . Nutrition in phenylketonuria. Mol Genet Metab 2011; 104, S10–S18.

    Article  CAS  Google Scholar 

  3. Pratt OE . A new approach to the treatment of phenylketonuria. J Ment Defic Res 1980; 24: 203–217.

    CAS  PubMed  Google Scholar 

  4. Pardridge WM . Blood-brain barrier carrier-mediated transport and brain metabolism of amino acids. Neurochem Res 1998; 23: 635–644.

    Article  CAS  Google Scholar 

  5. Daenzer M, Petzke KJ, Bequette BJ, Metges CC . Whole-body nitrogen and splanchnic amino acid metabolism differ in rats fed mixed diets containing casein or its corresponding amino acid mixture. J Nutr 2001; 131: 1965–1972.

    Article  CAS  Google Scholar 

  6. Gropper SS, Acosta PB . Effect of simultaneous ingestion of L-amino acids and whole protein on plasma amino acid and urea nitrogen concentrations in humans. JPEN J Parenter Enteral Nutr 1991; 15: 48–53.

    Article  CAS  Google Scholar 

  7. Hennermann JB, Roloff S, Gellermann J, Vollmer I, Windt E, Vetter B et al. Chronic kidney disease in adolescent and adult patients with phenylketonuria. J Inherit Metab Dis 2013; 36: 747–756.

    Article  CAS  Google Scholar 

  8. Doultani S, Turhan KN, Etzel MR . Whey protein isolate and glyco-macropeptide recovery from whey using ion exchange chromatography. J Food Sci 2003; 68: 1389–1395.

    Article  CAS  Google Scholar 

  9. Pena MJ, de Almeida MF, van Dam E, Ahring K, Belanger-Quintana A, Dokoupil K et al. Protein substitutes for phenylketonuria in Europe: access and nutritional composition. Eur J Clin Nutr 2016; 70: 785–789.

    Article  CAS  Google Scholar 

  10. Lim K, van Calcar SC, Nelson KL, Gleason ST, Ney DM . Acceptable low-phenylalanine foods and beverages can be made with glycomacropeptide from cheese whey for individuals with PKU. Mol Genet Metab 2007; 92: 176–178.

    Article  CAS  Google Scholar 

  11. Ney DM, Stroup BM, Clayton MK, Murali SG, Rice GM, Rohr F et al. Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial. Am J Clin Nutr 2016; 104: 334–345.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. Sawin EA, De Wolfe TJ, Aktas B, Stroup BM, Murali SG, Steele JL et al. Glycomacropeptide is a prebiotic that reduces Desulfovibrio bacteria, increases cecal short-chain fatty acids, and is anti-inflammatory in mice. Am J Physiol Gastrointest Liver Physiol 2015; 309: G590–G601.

    Article  CAS  Google Scholar 

  15. Solverson P, Murali SG, Litscher SJ, Blank RD, Ney DM . Low bone strength is a manifestation of phenylketonuria in mice and is attenuated by a glycomacropeptide diet. PLoS One 2012; 7: e45165.

    Article  CAS  Google Scholar 

  16. MacLeod EL, Clayton MK, van Calcar SC, Ney DM . Breakfast with glycomacropeptide compared with amino acids suppresses plasma ghrelin levels in individuals with phenylketonuria. Mol Genet Metab 2010; 100: 303–308.

    Article  CAS  Google Scholar 

  17. Solverson P, Murali SG, Brinkman AS, Nelson DW, Clayton MK, Yen CL et al. Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria. Am J Physiol Endocrinol Metab 2012; 302: E885–E895.

    Article  CAS  Google Scholar 

  18. Ney DM, Gleason ST, van Calcar SC, MacLeod EL, Nelson KL, Etzel MR et al. Nutritional management of PKU with glycomacropeptide from cheese whey. J Inherit Metab Dis 2009; 32: 32–39.

    Article  CAS  Google Scholar 

  19. Rocha JC, Vilarinho L, Cabral A, Osório RV, Almeida MF . Consensus for the nutritional treatment of phenylketonuria. Acta Pediatr Portuguesa 2007; 38: 44–54.

    Google Scholar 

  20. Kyle UG, Bosaeus I, De Lorenzo AD, Deurenberg P, Elia M, Manuel Gomez J et al. Bioelectrical impedance analysis-part II: utilization in clinical practice. Clin Nutr 2004; 23: 1430–1453.

    Article  Google Scholar 

  21. 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, S40–S43.

    Article  CAS  Google Scholar 

  22. Rocha JC, van Spronsen FJ, Almeida MF, Soares G, Quelhas D, Ramos E et al. Dietary treatment in phenylketonuria does not lead to increased risk of obesity or metabolic syndrome. Mol Genet Metab 2012; 107: 659–663.

    Article  CAS  Google Scholar 

  23. Sun SS, Chumlea WC, Heymsfield SB, Lukaski HC, Schoeller D, Friedl K et al. Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys. Am J Clin Nutr 2003; 77: 331–340.

    Article  CAS  Google Scholar 

  24. Chiolero A, Bovet P, Paradis G, Paccaud F . Has Blood Pressure Increased in Children in Response to the Obesity Epidemic? Pediatrics 2007; 119: 544–553.

    Article  Google Scholar 

  25. Mourad A, Carney S, Gillies A, Jones B, Nanra R, Trevillian P . Arm position and blood pressure: a risk factor for hypertension? J Hum Hypertens 2003; 17: 389–395.

    Article  CAS  Google Scholar 

  26. Netea RT, Lenders JWM, Smits P, Thien T . Both body and arm position significantly influence blood pressure measurement. J Hum Hypertens 2003; 17: 459–462.

    Article  CAS  Google Scholar 

  27. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 2006; 450: 76–85.

    Google Scholar 

  28. de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J . Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Org 2007; 85: 660–667.

    Article  Google Scholar 

  29. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 1995; 854: 1–452.

  30. MacDonald A, Gokmen-Ozel H, van Rijn M, Burgard P . The reality of dietary compliance in the management of phenylketonuria. J Inherit Metab Dis 2010; 33: 665–670.

    Article  Google Scholar 

  31. Yano S, Moseley K, Azen C . Melatonin and dopamine as biomarkers to optimize treatment in phenylketonuria: effects of tryptophan and tyrosine supplementation. J Pediatr 2014; 165: 184–189.e1.

    Article  CAS  Google Scholar 

  32. Luciana M, Sullivan J, Nelson CA . Associations between phenylalanine-to-tyrosine ratios and performance on tests of neuropsychological function in adolescents treated early and continuously for phenylketonuria. Child Dev 2001; 72: 1637–1652.

    Article  CAS  Google Scholar 

  33. Sharman R, Sullivan K, Young R, McGill J . A preliminary investigation of the role of the phenylalanine:tyrosine ratio in children with early and continuously treated phenylketonuria: toward identification of ‘safe’ levels. Dev Neuropsychol 2010; 35: 57–65.

    Article  Google Scholar 

  34. Jahja R, Huijbregts SC, de Sonneville LM, van der Meere JJ, van Spronsen FJ . Neurocognitive evidence for revision of treatment targets and guidelines for phenylketonuria. J Pediatr 2014; 164: 895–9.e2.

    Article  CAS  Google Scholar 

  35. Robbins TW, Arnsten AF . The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci 2009; 32: 267–287.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Author contributions

All the authors were involved in data collection, interpretation of data, critical revision of the paper for important intellectual content and final approval of the version to be published. AP was involved in project design, collection of data, data analysis and writing of the manuscript. JCR was involved in project design, data analysis and writing of the manuscript.

Author information

Authors and Affiliations

  1. Centro de Genética Médica, Centro Hospitalar do Porto (CHP), Porto, Portugal

    A Pinto, M F Almeida, P C Ramos & J C Rocha

  2. Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto-UMIB/ICBAS/UP, Porto, Portugal

    M F Almeida

  3. Unidade de Doenças Metabólicas, Centro Hospitalar do Porto (CHP), Porto, Portugal

    S Rocha, A Guimas, R Ribeiro, E Martins & A Bandeira

  4. Birmingham Children’s Hospital, Birmingham, UK

    A MacDonald

  5. Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal

    J C Rocha

  6. Centre for Health Technology and Services Research (CINTESIS), Porto, Portugal

    J C Rocha

Authors
  1. A Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M F Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P C Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Guimas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Bandeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A MacDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J C Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J C Rocha.

Ethics declarations

Competing interests

AP has received an educational grant from Cambrooke Therapeutics and grants from Vitaflo, Merck Serono and Biomarin to attend scientific meetings. MFA received grants from Glutamine, Nutricia, Merck Serono, Biomarin, Orphan and Lifediet to attend congress and for education. AM has received research funding and honoraria from Nutricia, Vitaflo International and Merck Serono. She is a member of the European Nutritionist Expert Panel (Biomarin), member of Sapropterin Advisory Board (Biomarin), member of the Advisory Board entitled ELEMENT (Danone-Nutricia) and member of an Advisory Board for Arla and Applied Pharma Research. JCR is member of the European Nutrition Expert Panel (Biomarin) and member of an Advisory Board for Applied Pharma Research. The remaining authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pinto, A., Almeida, M., Ramos, P. et al. Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source. Eur J Clin Nutr 71, 1230–1234 (2017). https://doi.org/10.1038/ejcn.2017.38

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2017.38

This article is cited by

Search

Advanced search

Quick links