Diet History Is a Reliable Predictor of Suboptimal Docosahexaenoic Acid Levels in Adult Patients with Phenylketonuria

  • T. Bosdet
  • J. BranovEmail author
  • C. Selvage
  • M. Yousefi
  • S. Sirrs
Research Report
Part of the JIMD Reports book series (JIMD, volume 21)


Background: Omega-3 long-chain polyunsaturated fatty acids (n3LCPUFA) levels are reduced in phenylketonuria (PKU). Recent care guidelines recommend essential fatty acid status is monitored in patients with PKU but access to such testing is limited. We hypothesized that information obtained on diet history would identify PKU adults with suboptimal levels of n3LCPUFA.

Methods: A 12-month single site prospective study was completed including 35 adults (age 18–46) attending a clinic for adults with inborn errors of metabolism. Levels of n3LCPUFA were correlated with estimated intake using a published food frequency questionnaire. n3LCPUFA levels were tested at a commercial laboratory and values > one SD below the laboratory mean value were considered suboptimal.

Results: Mean levels of docosahexaenoic acid (DHA) were lower and levels of eicosapentaenoic acid (EPA) and alpha-linoleic acid (ALA) higher in subjects with PKU than in laboratory controls. n3LCPUFA levels correlated with estimated intake (p <0.002). Diet history had a positive predictive value of 93% and negative predictive value of 90% to identify subjects with suboptimal n3LCPUFA levels.

Conclusions: Diet history is sufficient to predict adult subjects who may have low DHA levels and can be used to target testing or supplementation to those at risk. DHA levels are low despite high levels of ALA suggesting that supplementation, if indicated, should be with preformed DHA rather than with its precursors.


Docosahexaenoic Acid Diet History Specialized Laboratory Testing Nutrition Screening Tool Kennedy Krieger Institute 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Acosta PB, Yannicelli S, Singh R et al (2001) Intake and blood levels of fatty acids in treated patients with phenylketonuria. J Ped Gastroenterol Nutr 33:253–259CrossRefGoogle Scholar
  2. Agostoni C, Marangoni F, Riva E, Giovannini M, Galli C (1997) Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children negatively correlate with dietary compliance. Prostaglandins Leukot Essent Fatty Acids 56:219–222PubMedCrossRefGoogle Scholar
  3. Agostoni C, Verduci E, Massetto N, Radaelli G, Riva E, Giovannini M (2003) Plasma long-chain polyunsaturated fatty acids and neurodevelopment through the first 12 months of life in phenylketonuria. Develop Med Child Neurol 45:257–261PubMedCrossRefGoogle Scholar
  4. Beblo S, Reinhardt BS et al (2001) Fish oil supplementation improves visual evoked potentials in children with phenylketonuria. Neurology 57:1488–1491PubMedCrossRefGoogle Scholar
  5. Beblo S, Reinhardt, H, Demmelmair, Muntau AC, Koletzko B (2007) Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria. J Pediatr 150:479–484Google Scholar
  6. Berry SA, Brown C, Grant M et al (2013) Newborn screening 50 years later: access issues faced by adults with PKU. Genet Med 15:591–599PubMedCentralPubMedCrossRefGoogle Scholar
  7. Gutierrez-Mata AP, Vilaseca MA, Capdevila-Cirera A et al (2012) Neurological, neuropsychological, and ophthalmological evolution after one year of docosahexaenoic acid supplementation in phenylketonuric patients. Revista de Neurologia 55:200–206PubMedGoogle Scholar
  8. Infante JP, Huszagh VA (2001) Impaired arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acid synthesis by phenylalanine metabolites as etiological factors in the neuropathology of phenylketonuria. Mol Genet Metab 72:185–198PubMedCrossRefGoogle Scholar
  9. Koletzko B, Beblo S, Demmelmail H, Hanebutt FL (2009) Omega-3 LC-PUFA supply and neurological outcomes in children with phenylketonuria. J Pediatr Gastroent Nutr 48:S2–S7CrossRefGoogle Scholar
  10. Lage S, Bueno M, Andrade F et al (2010) Fatty acid profile in patients with phenylketonuria and its relationship with bone mineral density. J Inherit Metab Dis 33(Suppl 3):S363–S371PubMedCrossRefGoogle Scholar
  11. Lohner S, Fekete K, Decsi T (2013) Lower n-3 long-chain polyunsaturated fatty acid values in patients with phenylketonuria: a systematic review and meta-analysis. Nutr Res 33:513–520PubMedCrossRefGoogle Scholar
  12. Moseley K, Koch R, Moser AB (2002) Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet. J Inherit Metab Dis 25:56–64Google Scholar
  13. Pöge AP, Bäumann K, Müller E, Leichsenring M, Schmidt H, Bremer HJ (1998) Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake. J Inherit Metab Dis 21:373–381PubMedCrossRefGoogle Scholar
  14. Singh RA, Rohr F, Frazier D et al (2014) Recommendations for the nutrition management of phenylalanine hydroxylase deficiency. Genet Med 16:121–131PubMedCentralPubMedCrossRefGoogle Scholar
  15. Sublette ME, Segal-Isaacson CJ, Cooper TB et al (2011) Validation of a food frequency questionnaire to assess intake of n-3 polyunsaturated fatty acids in subjects with and without major depressive disorder. J Am Diet Assoc 111:117–123PubMedCentralPubMedCrossRefGoogle Scholar
  16. Vilaseca MA, Lambruschini N, Gómez-López L et al (2010) Long-chain polyunsaturated fatty acid status in phenylketonuric patients treated with tetrahydrobiopterin. Clin Biochem 43:411–415PubMedCrossRefGoogle Scholar
  17. Yi SHL, Kable JA, Evatt ML, Singh RH (2011) A cross-sectional study of docosahexaenoic acid status and cognitive outcomes in females of reproductive age with phenylketonuria. J Inherit Metab Dis 34:455–463PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • T. Bosdet
    • 1
  • J. Branov
    • 1
    Email author
  • C. Selvage
    • 1
  • M. Yousefi
    • 2
  • S. Sirrs
    • 1
  1. 1.Adult Metabolic Diseases Clinic, Vancouver HospitalVancouverCanada
  2. 2.Brain Research CenterUniversity of British ColumbiaVancouverCanada

Personalised recommendations