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Clinical Nutrition

Polyunsaturated fatty acid status in treated isovaleric acidemia patients

European Journal of Clinical Nutrition volume 70, pages 1123–1126 (2016)Cite this article

Subjects

Abstract

Background/Objectives:

Nutritional deficiencies are frequently observed when treating patients with inborn errors of metabolism due to an unbalanced diet. Thus far, patients with isovaleric acidemia (IVA) who adhere to a restricted protein diet have not been investigated in this respect. We hypothesize that these patients may have a polyunsaturated fatty acid (PUFA) deficiency, leading to potential clinical complications.

Subjects/Methods:

We examined the nutritional status by reporting on potential deficiencies in PUFAs in treated IVA patients. A general clinical chemistry work-up as well as gas chromatography flame ionization detector analysis was performed to determine PUFAs in the plasma of 10 IVA patients.

Results:

The general clinical chemistry tests did not indicate severe hematological abnormalities or nutritional insufficiencies. We identified a significant reduction in plasma PUFA levels, especially in omega-3 (all acids, P<0.001) and omega-6 (in particular 20:3n-6 P<0.0001 and 20:4n-6 P=0.0005) fatty acids. In addition, an elevation in omega-9 fatty acids, with the exception of 20:3n-9 and C22:1n-9, was not suggestive of complete essential fatty acid deficiency but rather indicative of isolated and/or combined omega-3 and omega-6 fatty acid depletion.

Conclusions:

This study emphasizes the potential nutritional insufficiencies that may occur because of therapeutic intervention in IVA.

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References

  1. Vockley J, Zschocke J, Knerr I, Vockley CW, Gibson KM. Branched chain organic acidurias. In: Valle D, Beaudet A, Vogelstein B, Kinzler KW (eds) The Online Metabolic and Molecular Bases of Inherited Disease, Part 8. McGraw-Hill: New York, NY, USA, 2012, Available at www.ommbid.com (accessed on 2 October 2012).

    Google Scholar 

  2. Grünert SC, Wendel U, Linder M, Leischsenring M, Schwab KO, Vockley J et al. Clinical and neurolocognitive outcome in symptomatic isovaleric academia. Orphanet J Rare Dis 2012; 7: 1–9.

    Article  Google Scholar 

  3. Giovannini M, Biasucci G, Luotti D, Fioir L, Riva E . Nutrition in children affected by inherited metabolic diseases. Ann Ist Super Sanità 1995; 31: 489–502.

    CAS  PubMed  Google Scholar 

  4. Robinson M, White FJ, Cleary MA, Wraith E, Lam WK, Walter JH . Increased risk of vitamin B12 deficiency in patients with phenylketonuria on an unrestricted or relaxed diet. J Pediatr 2000; 136: 545–547.

    Article  CAS  Google Scholar 

  5. Vlaardingerbroek H, Hornstra G, de Koning TJ, Smeitink JA, Bakker HD, de Klerk HB et al. Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism. Mol Genet Metab 2006; 88: 159–165.

    Article  CAS  Google Scholar 

  6. Fekete K, Decsi T . Long-chain polyunsaturated fatty acids in inborn errors of metabolism. Nutrients 2010; 2: 965–974.

    Article  CAS  Google Scholar 

  7. Jeppesen PB, Christensen MS, Høy C, Mortensen PB . Essential fatty acid deficiency in patients with severe fat malabsorption. Am J Clin Nutr 1997; 65: 837–843.

    Article  CAS  Google Scholar 

  8. Sprecher H . Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta 2000; 1486: 219–231.

    Article  CAS  Google Scholar 

  9. Duran M, Wanders RJA . Plasmalogens and polyunsaturated fatty acids. In: Blau N, Duran M, Gibson M (eds) Laboratory Guide to the Methods in Biochemical Genetics. Springer-Verlag Berlin: Heidelberg, 2004; 207–220.

    Google Scholar 

  10. Nakamura MT, Nara TY . Structure, function and dietary regulation of Δ6, Δ5, and Δ9 desaturases. Annu Rev Nutr 2004; 24: 354–376.

    Article  Google Scholar 

  11. Vognild E, Elveoll EO, Brox J, Olsen RL, Barstad H, Aursand M et al. Effects of dietary marine oils and olive oil on fatty acid composition, platelet membrane fluidity, platelet responses, and serum lipids in healthy humans. Lipids 1998; 33: 427–436.

    Article  CAS  Google Scholar 

  12. Benatti P, Peluso G, Nicolai R, Calvani M . Polyunsaturated fatty acids: Biochemical, nutritional and epigenetic properties. J Am Coll Nutr 2004; 23: 281–302.

    Article  CAS  Google Scholar 

  13. Von Schacky C, Fischer S, Weber PC . Long term effects of dietary marine ω-3 fatty acids upon plasma and cellular lipids, platelet function and eicosanoid formation in humans. J Clin Invest 1985; 76: 1626–163112.

    Article  CAS  Google Scholar 

  14. Lauritzen L, Hansen HS, Jorgensen MH, Michaelsen KF . The essentiality of long-chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001; 40: 1–90.

    Article  CAS  Google Scholar 

  15. Peters BD, Machielsen MW, Hoen WP, Caan MW, Malhotra AK, Szeszko PR et al. Polyunsaturated fatty acid concentration predicts myelin integrity in early-phase psychosis. Schizophr Bull 2013; 39: 830–838.

    Article  Google Scholar 

  16. Smith M, Scholey A . Nutritional influences on human neurocognitive functioning. Front Hum Neurosci 2014; 8: 358.

    PubMed  PubMed Central  Google Scholar 

  17. Hoen WP, Lijmer JG, Duran M, Wanders RJA, van Beveren NJM, de Haan L . Red blood cell polyunsaturated fatty acids measured in red blood cells and schizophrenia: A meta-analysis. Psychiatry Res 2013; 207: 1–12.

    Article  CAS  Google Scholar 

  18. Dercksen M, Koekemoer G, Duran M, Wanders RJA, Mienie LJ, Reinecke CJ . Organic acid profile of isovaleric acidemia: a comprehensive metabolomics approach. Metabolomics 2013; 9: 765–777.

    Article  CAS  Google Scholar 

  19. Dercksen M, Duran M, Ijlst L, Mienie LJ, Reinecke CJ, Ruiter JP et al. Clinical variability of isovaleric acidemia in a genetically homogeneous population. J Inherit Metab Dis 2012; 35: 1021–1029.

    Article  CAS  Google Scholar 

  20. Muskiet FA, van Doormaal JJ, Martini IA, Wolthers BG, van der Slik W . Capillary gas chromatographic profiling of total long-chain fatty acids and cholesterol in biological materials. J Chromatogr 1983; 278: 231–244.

    Article  CAS  Google Scholar 

  21. Tabachnick BG, Fidell LS . Using Multivariate Statistics, 6th ed. Pearson: Boston, MA, USA, 2013.

    Google Scholar 

  22. Simopoulos AP . Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 2006; 60: 502–507.

    Article  CAS  Google Scholar 

  23. Bazinet RP, Layé S . Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Rev Neurosci 2014; 15: 771–785.

    Article  CAS  Google Scholar 

  24. Fulco AJ, Mead JF . Metabolism of essential fatty acids VIII. Origins of 5,8,11-eicosatrienoic acid in fat-deficient mice. J Biol Chem 1959; 234: 1411–1416.

    CAS  PubMed  Google Scholar 

  25. Holman RT . The ratio of trienoic:tetraenoic acids in tissue lipids as a measure of essential fatty acid requirement. J Nutr 1960; 70: 405–410.

    Article  CAS  Google Scholar 

  26. Rasmussen M, Moser AB, Borel J, Moser HW . Brain erucic and very long chain fatty acid levels in adrenoleukodystrophy patients treated with glyceryl trioleated and trierucate oils (Lorenzo's oil). Neurochem Res 1994; 19: 1073–1082.

    Article  CAS  Google Scholar 

  27. Nettleton JA . Omega-3 Fatty Acids and Health. Chapman and Hall: New York, NY, USA, 1995.

    Book  Google Scholar 

  28. Cunnane SC . Problems with essential fatty acids: time for a new paradigm. Prog Lipid Res 2003; 42: 544–568.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was financially supported as a Carolina MacGillavry PhD Fellowship awarded by ‘Koninklijke Nederlandse Akademie van Wetenschappen’ to assist in research in Isovaleric acidemia. We thank the staff at the Laboratory Genetic Metabolic Diseases (GMDs) at the Academic Medical Center, University of Amsterdam, for their expert advice and assistance. The study was also made possible with the logistical, scientific and statistical contribution of the staff of Human Metabolomics and Wilma Breytenbach, the statistical consultant at the North-West University in Potchefstroom, South Africa. We are grateful to the patients and their families for participation in this study. Data presented at ICIEM 2013 and Submitted for publication.

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Authors and Affiliations

  1. Departments of Pediatrics and Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    M Dercksen, W Kulik, R J A Wanders & M Duran

  2. Human Metabolomics, North-West University, Potchefstroom, South Africa

    M Dercksen, L J Mienie & C J Reinecke

Authors
  1. M Dercksen
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  2. W Kulik
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  3. L J Mienie
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  4. C J Reinecke
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  5. R J A Wanders
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  6. M Duran
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Correspondence to M Dercksen.

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Dercksen, M., Kulik, W., Mienie, L. et al. Polyunsaturated fatty acid status in treated isovaleric acidemia patients. Eur J Clin Nutr 70, 1123–1126 (2016). https://doi.org/10.1038/ejcn.2016.100

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