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 Communication
  • Published:

Plasma thiols and their determinants in phenylketonuria

European Journal of Clinical Nutrition volume 57, pages 964–968 (2003)Cite this article

Abstract

Objective: Treatment of phenylketonuria (PKU) patients consists of a phenylalanine-restricted diet supplemented with a tyrosine-, vitamin- and oligoelement-enriched amino-acid mixture. Vitamins and oligoelements may be deficient when compliance with the supplemented special formula is poor. Plasma thiol concentrations (especially homocysteine) depend mainly on B-vitamin intake. Our aim was to evaluate the plasma thiol concentrations (homocysteine, cysteine and glutathione) and their determinants (methionine, cobalamin and folate) in PKU patients under dietary treatment compared with age-matched controls.

Design and setting: Cross-sectional study performed in a tertiary care Hospital.

Subjects: PKU (42) patients under dietary treatment compared with 42 age-matched controls.

Interventions: Plasma total homocysteine, cysteine and glutathione were analyzed by HPLC with fluorescence detection. Plasma phenylalanine and methionine were analyzed by ion exchange chromatography. Serum folate and cobalamin were analyzed by radioimmunoassay procedures.

Results: Total homocysteine concentrations were significantly lower in the PKU patients compared with the control group (Students t-test; P<0.0001). Serum folate and cobalamin were significantly higher in the PKU group (t-Student; P<0.0001) compared with controls. A significantly negative correlation was observed between total homocysteine and folate (r=−0.378; P=0.016), and between cobalamin and phenylalanine concentrations (r=−0.367; P=0.022) in the PKU group.

Conclusions: Plasma total homocysteine values are lower in the PKU group than in the controls, probably because of high folate values. High phenylalanine values, an indicator of poor dietary compliance, are negatively associated with cobalamin, which might be deficient in some cases.

Sponsorship: This work was supported by Grants FIS: 00/1056 and Marató TV3: 99/3710. C Colomé was the recipient of a grant from the Hospital Sant Joan de Déu to perform this 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

Similar content being viewed by others

References

  • Acosta PB & Yannicelli S (1999): Plasma micronutrient concentrations in infants undergoing for pheylketonuria. Biol. Trace Elem. Res. 67, 75–84.

    Article  CAS  Google Scholar 

  • Artuch R, Vilaseca MA, Moreno J, Lambruschini N, Cambra FJ & Campistol J (1999): Decreased serum ubiquinone-10 concentration in phenylketonuria. Am. J. Clin. Nutr. 70, 892–895.

    Article  CAS  Google Scholar 

  • Brenton DP & Pietz J (2000): Adult care in phenylketonuria and hyperphenylalaninemia: the relevance of neurological abnormalities. Eur. J. Pediatr. 159(Suppl 2), S114–S120.

    Article  Google Scholar 

  • Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B & Graham I (1991): Hyperhomocysteinemia: an independent risk factor for vascular disease. N. Engl. J. Med. 324, 1149–1155.

    Article  CAS  Google Scholar 

  • Colome C, Sierra C & Vilaseca MA (2000): Errores congénitos del metabolismo: causa de estrés oxidativo? Med. Clin. (Barc). 115, 111–117.

    Article  CAS  Google Scholar 

  • Colomé C, Artuch R, Vilaseca MA, Sierra C, Brandi N, Cambra FJ, Lambruschini N & Campistol J (2002): Ubiquinone-10 content in lymphocytes of phenylketonuric patients. Clin. Biochem. 35, 81–84.

    Article  Google Scholar 

  • Darling G, Mathias P, O'Regan M & Naughten E (1992): Serum selenium levels in individuals on PKU diets. J. Inherit. Metab. Dis. 15, 769–773.

    Article  CAS  Google Scholar 

  • El-Khairy L, Ueland, PM, Refsum H, Graham MI & Vollset SE, European Concerted Action Project (2001): Plasma total cysteine as a risk factor for vascular disease: The European Concerted Action Project. Circulation 103, 2544–2549.

    Article  CAS  Google Scholar 

  • Guttormsen AB, Ueland PM, Nesthus I, Nygard O, Schneede J, Vollset SE & Refsum H (1996): Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (&gt; or =40 micromol/liter). The Hordaland Homocysteine Study. J. Clin. Invest. 98, 2174–2183.

    Article  CAS  Google Scholar 

  • Hanley WB, Feigenbaum AS, Clarke JT, Schoonheyt WE & Austin V (1996): Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur. J. Pediatr. 155, S145–S147.

    Article  Google Scholar 

  • Loscalzo J (1996): The oxidant stress of hyperhomocysteinemia. J. Clin. Invest. 98, 5–7.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Roediger WEW (1995): New views on the pathogenesis of Kwashiorkor: methionine and other amino acids. J. Pediatr. Gastroenterol. Nutr. 21, 130–136.

    Article  CAS  Google Scholar 

  • Rosenblatt DS & Fenton WA (2001): Inherited disorders of folate and cobalamin transport and metabolism. In The Metabolic and Molecular Bases of Inherited Disease, 8th Edition, eds CR Scriver, AL Beaudet, WS Sly & WS D Valle, pp 3897–3933. New York: McGraw-Hill.

    Google Scholar 

  • Schneede J, Refsum H & Ueland PM (2000): Biological and environmental determinants of plasma homocysteine. Semin. Thromb. Hemost. 26, 263–279.

    Article  CAS  Google Scholar 

  • Scriver CR Kaufman, Eisensmith RC & Woo SLC (1995): The hyperphenylalaninemias. In The Metabolic and Molecular Basis of Inherited Disease, 7th Edition, eds CR Scriver, AL Beaudet, WS Sly, & D Valle, pp 1015–1075. New York: McGraw Hill.

    Google Scholar 

  • Sierra C, Vilaseca MA, Moyano D, Brandi N, Campistol J, Lambruschini N, Cambra FJ, Deulofeu R & Mira A (1998): Antioxidant status in hyperphenylalaninemia. Clin. Chim. Acta 276, 1–9.

    Article  CAS  Google Scholar 

  • Siri PW, Verhoef P & Kok FJ (1998): Vitamins B6, B12 and folate: association with plasma total homocysteine and risk of coronary atherosclerosis. J. Am. Coll. Nutr. 17, 435–441.

    Article  CAS  Google Scholar 

  • Van Bakel MM, Printzen G, Wermuth B & Wiesmann UN (2000): Antioxidant and thyroid hormone status in selenium-deficient phenylketonuric and hyperphenylalaninemic patients. Am. J. Clin. Nutr. 72, 976–981.

    Article  CAS  Google Scholar 

  • Vilaseca MA, Moyano D, Ferrer I & Artuch R (1997): Total homocysteine in pediatric patients. Clin. Chem. 43, 690–692.

    CAS  PubMed  Google Scholar 

  • Wendel U, Ullrich K, Schmidt H & Batzler U (1990): Six-year follow up of phenylalanine intakes and plasma phenylalanine concentrations. Eur. J. Pediatr. 149, S13–S16.

    Article  Google Scholar 

  • White AC, Thannickal VJ & Fanburg BL (1994): Glutathione deficiency in human disease. J. Nutr. Biochem. 5, 218–226.

    Article  CAS  Google Scholar 

  • Wilke BC, Vidailhet M, Favier A, Guillemin C, Ducros V, Arnaud J & Richard MJ (1992): Selenium glutathione peroxidase (GSH-Px) and lipid peroxidation products before and after selenium supplementation. Clin. Chim. Acta 207, 137–142.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are very grateful to Julia Pineda, Rosa Maria Puig and Joan Moreno for their skillful technical assistance.

Author information

Authors and Affiliations

  1. Biochemistry Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

    C Colomé, R Artuch, C Sierra, N Brandi & M-A Vilaseca

  2. Pediatrics Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

    N Lambruschini

  3. Neurology Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain

    J Campistol

Authors
  1. C Colomé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Artuch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Sierra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Brandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Lambruschini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Campistol
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M-A Vilaseca
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Guarantor: R Artuch.

Contributors: CC, RA and M-AV made the plasma amino acids and thiol determinations, the statistical analysis, and wrote the paper. CS and NB performed the glutathione analysis, created the data bases and collaborated in writing the paper. NL was in charge of the dietary management and JC of the neurological evaluation of PKU patients, and critically reviewed the contents of the manuscript.

Corresponding author

Correspondence to R Artuch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Colomé, C., Artuch, R., Sierra, C. et al. Plasma thiols and their determinants in phenylketonuria. Eur J Clin Nutr 57, 964–968 (2003). https://doi.org/10.1038/sj.ejcn.1601631

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601631

Keywords

This article is cited by

Search

Advanced search

Quick links