European Journal of Pediatrics

, Volume 174, Issue 1, pp 119–127 | Cite as

Management of adult patients with phenylketonuria: survey results from 24 countries

  • Friedrich K. TrefzEmail author
  • Francjan J. van Spronsen
  • Anita MacDonald
  • François Feillet
  • Ania C. Muntau
  • Amaya Belanger-Quintana
  • Alberto Burlina
  • Mübeccel Demirkol
  • Marcello Giovannini
  • Christoph Gasteyger
Original Article


Phenylketonuria (PKU) is no longer considered merely a pediatric concern; current guidelines recommend life-long treatment. However, information on the adult PKU patient population is scarce. A survey was initiated on behalf of the European PKU Group (EPG) that focused specifically on early-treated adult patients diagnosed by neonatal screening. The online survey was sent via email to 204 healthcare professionals (HCPs) in 33 countries. Eighty-one HCPs from 24 countries responded. The main findings were that the majority of adult patients with PKU in active follow-up are under 30 years of age and are managed in centers that also treat children. Seventy-eight percent of adult PKU patients in follow-up receive treatment, mainly by diet (71 %), with BH4 treatment rarely used in adulthood. Only 26 % of responding HCPs perform routine neurocognitive testing in all their adult patients. There was little consensus regarding target blood phenylalanine (Phe) concentrations, although the majority of respondents reported that their patients achieved blood Phe concentrations below 1200 μmol/l.

Conclusion: This survey highlights the need for blood Phe concentration target recommendations and consensus guidelines, more research into adult PKU patient management, and the need to identify those patients lost to follow-up to ensure PKU is managed for life.


Phenylketonuria Phenylalanine Survey Adults Diet 





Inherited metabolic disease







This study was sponsored by Merck Serono, a division of Merck KGaA, Darmstadt, Germany. The authors would like to thank Physicians World Europe GmbH (supported by Merck Serono a division of Merck KGaA, Darmstadt, Germany) for data analyses and editorial assistance, and their PKU colleagues that took the time to respond to the survey for their valuable support of this project.

Conflict of interests

All authors apart from Mübeccel Demirkol and Christoph Gasteyger are members of the European PKU Group (EPG), an Advisory Board to Merck Serono. Christoph Gasteyger was an employee of Merck Serono, a division of Merck KGaA, Darmstadt, Germany. Anita MacDonald and Amaya Belanger-Quintana are members of the European Nutritionist Expert Panel in PKU (ENEP), an Advisory Board to Merck Serono. Anita MacDonald and Francjan J. van Spronsen provide consultancy to Danone. Anita MacDonald also receives research support from Vitaflo.

Authors’ contributions

All authors contributed to the conception, design, analysis and interpretation of the content, manuscript preparation, and revision and have read and approved the final version of the manuscript.

Supplementary material

431_2014_2458_MOESM1_ESM.pdf (70 kb)
ESM 1 (PDF 70 kb)


  1. 1.
    Ahring K, Belanger-Quintana A, Dokoupil K, Gokmen-Ozel H, Lammardo AM, MacDonald A, Motzfeldt K, Nowacka M, Robert M, van Rijn M (2011) Blood phenylalanine control in phenylketonuria: a survey of 10 European centres. Eur J Clin Nutr 65(2):275–278. doi: 10.1038/ejcn.2010.258 PubMedCrossRefGoogle Scholar
  2. 2.
    Bates LM, Hankivsky O, Springer KW (2009) Gender and health inequities: a comment on the final report of the WHO commission on the social determinants of health. Soc Sci Med 69(7):1002–1004. doi: 10.1016/j.socscimed.2009.07.021 PubMedCrossRefGoogle Scholar
  3. 3.
    Bik-Multanowski M, Didycz B, Mozrzymas R, Nowacka M, Kaluzny L, Cichy W, Schneiberg B, Amilkiewicz J, Bilar A, Gizewska M, Lange A, Starostecka E, Chrobot A, Wojcicka-Bartlomiejczyk BI, Milanowski A (2008) Quality of life in noncompliant adults with phenylketonuria after resumption of the diet. J Inherit Metab Dis 31(Suppl 2):S415–418. doi: 10.1007/s10545-008-0978-7 PubMedCrossRefGoogle Scholar
  4. 4.
    Blau N, Belanger-Quintana A, Demirkol M, Feillet F, Giovannini M, MacDonald A, Trefz FK, van Spronsen F, European PKUc (2010) Management of phenylketonuria in Europe: survey results from 19 countries. Mol Genet Metab 99(2):109–115. doi: 10.1016/j.ymgme.2009.09.005 PubMedCrossRefGoogle Scholar
  5. 5.
    Blau N, Hennermann JB, Langenbeck U, Lichter-Konecki U (2011) Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies. Mol Genet Metab 104(Suppl):S2–9. doi: 10.1016/j.ymgme.2011.08.017 PubMedCrossRefGoogle Scholar
  6. 6.
    Burton BK, Leviton L (2010) Reaching out to the lost generation of adults with early-treated phenylketonuria (PKU). Mol Genet Metab 101(2–3):146–148. doi: 10.1016/j.ymgme.2010.06.006 PubMedCrossRefGoogle Scholar
  7. 7.
    Cazzorla C, Del Rizzo M, Burgard P, Zanco C, Bordugo A, Burlina AB, Burlina AP (2012) Application of the WHOQOL-100 for the assessment of quality of life of adult patients with inherited metabolic diseases. Mol Genet Metab 106(1):25–30. doi: 10.1016/j.ymgme.2012.02.008 PubMedCrossRefGoogle Scholar
  8. 8.
    Cleary M, Walter JH (2001) Assessment of adult phenylketonuria. Ann Clin Biochem 38(Pt 5):450–458PubMedCrossRefGoogle Scholar
  9. 9.
    Dawson C, Murphy E, Maritz C, Chan H, Ellerton C, Carpenter RH, Lachmann RH (2011) Dietary treatment of phenylketonuria: the effect of phenylalanine on reaction time. J Inherit Metab Dis 34(2):449–454. doi: 10.1007/s10545-010-9276-2 PubMedCrossRefGoogle Scholar
  10. 10.
    Demirkol M, Gizewska M, Giovannini M, Walter J (2011) Follow up of phenylketonuria patients. Mol Genet Metab 104(Suppl):S31–39. doi: 10.1016/j.ymgme.2011.08.005 PubMedCrossRefGoogle Scholar
  11. 11.
    Hanley WB (2004) Adult phenylketonuria. Am J Med 117(8):590–595. doi: 10.1016/j.amjmed.2004.03.042 PubMedCrossRefGoogle Scholar
  12. 12.
    Hoffmann B, Dragano N, Schweitzer-Krantz S (2012) Living situation, occupation and health-related quality of life in adult patients with classic galactosemia. J Inherit Metab Dis. doi: 10.1007/s10545-012-9469-y Google Scholar
  13. 13.
    Koch R, Burton B, Hoganson G, Peterson R, Rhead W, Rouse B, Scott R, Wolff J, Stern AM, Guttler F, Nelson M, de la Cruz F, Coldwell J, Erbe R, Geraghty MT, Shear C, Thomas J, Azen C (2002) Phenylketonuria in adulthood: a collaborative study. J Inherit Metab Dis 25(5):333–346PubMedCrossRefGoogle Scholar
  14. 14.
    Merrick J, Aspler S, Schwarz G (2003) Phenylalanine-restricted diet should be life long. A case report on long-term follow-up of an adolescent with untreated phenylketonuria. Int J Adolesc Med Health 15(2):165–168PubMedGoogle Scholar
  15. 15.
    Mutze U, Roth A, Weigel JF, Beblo S, Baerwald CG, Buhrdel P, Kiess W (2011) Transition of young adults with phenylketonuria from pediatric to adult care. J Inherit Metab Dis 34(3):701–709. doi: 10.1007/s10545-011-9284-x PubMedCrossRefGoogle Scholar
  16. 16.
    National Institutes of Health Consensus Development P (2001) National institutes of health consensus development conference statement: phenylketonuria: screening and management, October 16–18, 2000. Pediatrics 108(4):972–982CrossRefGoogle Scholar
  17. 17.
    Prick BW, Hop WC, Duvekot JJ (2012) Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: pregnancy complications and neonatal sequelae in untreated and treated pregnancies. Am J Clin Nutr 95(2):374–382. doi: 10.3945/ajcn.110.009456 PubMedCrossRefGoogle Scholar
  18. 18.
    Rutishauser C, Akre C, Suris JC (2011) Transition from pediatric to adult health care: expectations of adolescents with chronic disorders and their parents. Eur J Pediatr 170(7):865–871. doi: 10.1007/s00431-010-1364-7 PubMedCrossRefGoogle Scholar
  19. 19.
    Schwarz M, Wendel U (2005) Inborn errors of metabolism (IEM) in adults. A new challenge to internal medicine. Medizinische Klinik (Munich, Germany : 1983) 100(9):547–552. doi: 10.1007/s00063-005-1075-4 CrossRefGoogle Scholar
  20. 20.
    Scriver CR, Lee PJ (2004) The last day of the past is the first day of the future: transitional care for genetic patients. Am J Med 117(8):615–617. doi: 10.1016/j.amjmed.2004.08.002 PubMedCrossRefGoogle Scholar
  21. 21.
    ten Hoedt AE, de Sonneville LM, Francois B, ter Horst NM, Janssen MC, Rubio-Gozalbo ME, Wijburg FA, Hollak CE, Bosch AM (2011) 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 34(1):165–171. doi: 10.1007/s10545-010-9253-9 PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Trefz F, Maillot F, Motzfeldt K, Schwarz M (2011) Adult phenylketonuria outcome and management. Mol Genet Metab 104(Suppl):S26–30. doi: 10.1016/j.ymgme.2011.08.025 PubMedCrossRefGoogle Scholar
  23. 23.
    van Spronsen FJ, Burgard P (2008) The truth of treating patients with phenylketonuria after childhood: the need for a new guideline. J Inherit Metab Dis 31(6):673–679. doi: 10.1007/s10545-008-0918-6 PubMedCrossRefGoogle Scholar
  24. 24.
    Vockley J, Andersson HC, Antshel KM, Braverman NE, Burton BK, Frazier DM, Mitchell J, Smith WE, Thompson BH, Berry SA, American College of Medical G, Genomics Therapeutics C (2014) Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med Off J Am College Med Genet 16(2):188–200. doi: 10.1038/gim.2013.157 Google Scholar
  25. 25.
    Waisbren S, White DA (2010) Screening for cognitive and social-emotional problems in individuals with PKU: tools for use in the metabolic clinic. Mol Genet Metab 99(Suppl 1):S96–99. doi: 10.1016/j.ymgme.2009.10.006 PubMedCrossRefGoogle Scholar
  26. 26.
    Walter JH, White FJ, Hall SK, MacDonald A, Rylance G, Boneh A, Francis DE, Shortland GJ, Schmidt M, Vail A (2002) How practical are recommendations for dietary control in phenylketonuria? Lancet 360(9326):55–57PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Friedrich K. Trefz
    • 1
    Email author
  • Francjan J. van Spronsen
    • 2
  • Anita MacDonald
    • 3
  • François Feillet
    • 4
  • Ania C. Muntau
    • 5
  • Amaya Belanger-Quintana
    • 6
  • Alberto Burlina
    • 7
  • Mübeccel Demirkol
    • 8
  • Marcello Giovannini
    • 9
  • Christoph Gasteyger
    • 10
    • 11
  1. 1.Kreiskliniken Reutlingen GmbH, School of Medicine, Outpatient Medical CentreUniversity of TuebingenGammertingenGermany
  2. 2.Department of Paediatrics, Division of Metabolic Diseases, Beatrix Children’s HospitalUniversity Medical Centre GroningenGroningenThe Netherlands
  3. 3.The Children’s HospitalBirminghamUnited Kingdom
  4. 4.Hôpital d’enfants BraboisParisFrance
  5. 5.University Children’s Hospital, Medical Centre Hamburg EppendorfHamburgGermany
  6. 6.Hospital Ramon y CajalMadridSpain
  7. 7.Division of Inherited Metabolic DiseasesUniversity HospitalPaduaItaly
  8. 8.Department of Paediatrics, Division of Nutrition and Metabolism, Istanbul Faculty of Medicine, Children’s HospitalIstanbul UniversityIstanbulTurkey
  9. 9.Department of Paediatrics, San Paolo HospitalUniversity of MilanMilanItaly
  10. 10.Merck Serono a division of Merck KGaADarmstadtGermany
  11. 11.Alexion Pharmaceuticals, IncZürichSwitzerland

Personalised recommendations