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Nutritional issues in treating phenylketonuria

  • Advances and Challenges in PKU
  • Published:
Journal of Inherited Metabolic Disease

Abstract

A phenylalanine (Phe)-restricted diet is the mainstay of phenylketonuria (PKU) treatment, and, in recent years, the nutritional management of PKU has become more complex in order to optimize patients’ growth, development and diet compliance. Dietary restriction of Phe creates a diet similar to a vegan diet, and many of the nutritional concerns and questions applicable to vegans who wish to avoid animal products are also relevant to patients with PKU. Owing to their nutritional characteristics, breast milk and breastfeeding should be given greater consideration as a useful food in patients with PKU and in those with other inborn errors of metabolism. Further key issues for consideration include the quality of the available amino acid substitutes, the neurotrophic and neuroprotective effects of added long-chain polyunsaturated fatty acids (e.g. docosahexaenoic acid), micronutrient deficiencies, bone disease and antioxidant status. Long-term dietary guidance and monitoring of the nutritional status of patients with PKU should be part of a follow-up programme that continues for life.

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Abbreviations

AA:

arachidonic acid

DHA:

docosahexaenoic acid

Ig:

immunoglobulin

LCPUFA:

long-chain polyunsaturated fatty acid

LDL:

low-density lipoprotein

OMIM:

Online Mendelian Inheritance in Man database

Phe:

phenylalanine

PKU:

phenylketonuria

PUFA:

polyunsaturated fatty acid

References

  • Agostoni C, Verduci E, Fiori L, Riva E, Giovannini M (2000a) Breastfeeding rates among hyperphenylalaninemic infants. Acta Paediatr 89:366–367

    Article  CAS  PubMed  Google Scholar 

  • Agostoni C, Massetto N, Biasucci G et al (2000b) Effects of long-chain polyunsaturated fatty acid supplementation on fatty acid status and visual function in treated children with hyperphenylalaninemia. J Pediatr 137:504–509

    Article  CAS  PubMed  Google Scholar 

  • Agostoni C, Verduci E, Massetto N, Radaelli G, Riva E, Giovannini M (2003a) Plasma long-chain polyunsaturated fatty acids and neurodevelopment through the first 12 months of life in phenylketonuria. Dev Med Child Neurol 45:257–261

    Article  PubMed  Google Scholar 

  • Agostoni C, Verduci E, Massetto N et al (2003b) Long term effects of long chain polyunsaturated fats in hyperphenylalaninemic children. Arch Dis Child 88:582–583

    Article  CAS  PubMed  Google Scholar 

  • Agostoni C, Harvie A, McCulloch DL et al (2006) A randomized trial of long-chain polyunsaturated fatty acid supplementation in infants with phenylketonuria. Dev Med Child Neurol 48:207–212

    Article  PubMed  Google Scholar 

  • Agostoni C, Decsi T, Fewtrell M et al (2008) Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 46:99–110

    Article  PubMed  Google Scholar 

  • Al-Qadreh A, Schulpis KH, Athanasopoulou H, Mengreli C, Skarpalezou A, Voskaki I (1998) Bone mineral status in children with phenylketonuria under treatment. Acta Paediatr 87:1162–1166

    Article  CAS  PubMed  Google Scholar 

  • Ambroszkiewicz J, Gajewska J, Chelchowska M et al (2008) Concentration of osteoprotegerin, bone formation and resorption markers in patients with phenylketonuria (in Polish). Pol Merkuriusz Lek 25:57–60

    CAS  Google Scholar 

  • American Dietetic Association, Dietitians of Canada (2003) Position of the American Dietetic Association and Dietitians of Canada: vegetarian diets. Can J Diet Pract Res 64:62–81

    Article  Google Scholar 

  • Anderson JW, Johnstone BM, Remley DT (1999) Breast-feeding and cognitive development: a meta-analysis. Am J Clin Nutr 70:525–535

    CAS  PubMed  Google Scholar 

  • Artuch R, Colomé C, Sierra C et al (2004) A longitudinal study of antioxidant status in phenylketonuric patients. Clin Biochem 37:198–203

    Article  CAS  PubMed  Google Scholar 

  • Barat P, Barthe N, Redonnet-Vernhet I, Parrot F (2002) The impact of the control of serum phenylalanine levels on osteopenia in patients with phenylketonuria. Eur J Pediatr 161:687–688

    Article  CAS  PubMed  Google Scholar 

  • Bazan NG (2007) Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr Opin Clin Nutr Metab Care 10:136–141

    Article  CAS  PubMed  Google Scholar 

  • Beblo S, Reinhardt H, Muntau AC, Mueller-Felber W, Roscher AA, Koletzko B (2001) Fish oil supplementation improves visual evoked potentials in children with phenylketonuria. Neurology 57:1488–1491

    CAS  PubMed  Google Scholar 

  • Beblo S, Reinhardt H, Demmelmair H, 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 150:479–484

    Article  CAS  PubMed  Google Scholar 

  • Cleary MA, Feillet F, White FJ et al (2006) Randomised controlled trial of essential fatty acid supplementation in phenylketonuria. Eur J Clin Nutr 60:915–920

    Article  CAS  PubMed  Google Scholar 

  • Colomé C, Sierra C, Vilaseca MA (2000) Congenital errors of metabolism: cause of oxidative stress? Med Clin (Barc) 115:111–117

    Google Scholar 

  • Colomé C, Artuch R, Vilaseca MA et al (2002) Ubiquinone-10 content in lymphocytes of phenylketonuric patients. Clin Biochem 35:81–84

    Article  PubMed  Google Scholar 

  • Dagnelie PC, van Staveren WA (1994) Macrobiotic nutrition and child health: results of a population-based, mixed-longitudinal cohort study in The Netherlands. Am J Clin Nutr 59(5 Suppl):1187S–1196S

    CAS  PubMed  Google Scholar 

  • Fusco D, Colloca G, Lo Monaco MR, Cesari M (2007) Effects of antioxidant supplementation on the aging process. Clin Interv Aging 2:377–387

    CAS  PubMed  Google Scholar 

  • Galli C, Agostoni C, Mosconi C, Riva E, Salari PC, Giovannini M (1991) Reduced plasma C-20 and C-22 polyunsaturated fatty acids in children with phenylketonuria during dietary intervention. J Pediatr 119:562–567

    Article  CAS  PubMed  Google Scholar 

  • Gutteridge JM, Halliwell B (2000) Free radicals and antioxidants in the year 2000. A historical look to the future. Ann N Y Acad Sci 899:136–147

    Article  CAS  PubMed  Google Scholar 

  • Huner G, Baykal T, Demir F, Demirkol M (2005) Breastfeeding experience in inborn errors of metabolism other than phenylketonuria. J Inherit Metab Dis 28:457–465

    Article  CAS  PubMed  Google Scholar 

  • Hvas AM, Nexo E, Nielsen JB (2006) Vitamin B12 and vitamin B6 supplementation is needed among adults with phenylketonuria (PKU). J Inherit Metab Dis 29:47–53

    Article  CAS  PubMed  Google Scholar 

  • Karlsson KM, Karlsson C, Ahlborg HG, Valdimarsson O, Ljunghall S, Obrant KJ (2003) Bone turnover responses to changed physical activity. Calcif Tissue Int 72:675–680

    Article  CAS  PubMed  Google Scholar 

  • Koletzko B, Lien E, Agostoni C et al (2008) The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med 36:5–14

    Article  CAS  PubMed  Google Scholar 

  • MacDonald A, Ferguson C, Rylance G et al (2003) Are tablets a practical source of protein substitute in phenylketonuria? Arch Dis Child 88:327–329

    Article  CAS  PubMed  Google Scholar 

  • MacDonald A, Lilburn M, Cochrane B et al (2004) A new, low-volume protein substitute for teenagers and adults with phenylketonuria. J Inherit Metab Dis 27:127–135

    Article  CAS  PubMed  Google Scholar 

  • MacDonald A, Depondt E, Evans S et al (2006a) Breastfeeding in IMD. J Inherit Metab Dis 29:299–303

    Article  CAS  PubMed  Google Scholar 

  • MacDonald A, Lilburn M, Davies P et al (2006b) ‘Ready to drink’ protein substitute is easier is for people with phenylketonuria. J Inherit Metab Dis 29:526–531

    Article  CAS  PubMed  Google Scholar 

  • Mangels AR, Messina V (2001) Considerations in planning vegan diets: infants. J Am Diet Assoc 101:670–677

    Article  CAS  PubMed  Google Scholar 

  • McCarty MF (2001) Does a vegan diet reduce risk for Parkinson’s disease? Med Hypotheses 57:318–323

    Article  CAS  PubMed  Google Scholar 

  • Messina V, Mangels AR (2001) Considerations in planning vegan diets: children. J Am Diet Assoc 101:661–669

    Article  CAS  PubMed  Google Scholar 

  • Millet P, Vilaseca MA, Valls C et al (2005) Is deoxypyridinoline a good resorption marker to detect osteopenia in phenylketonuria? Clin Biochem 38:1127–1132

    Article  CAS  PubMed  Google Scholar 

  • Modan-Moses D, Vered I, Schwartz G et al (2007) Peak bone mass in patients with phenylketonuria. J Inherit Metab Dis 30:202–208

    Article  CAS  PubMed  Google Scholar 

  • 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 25:56–64

    Article  CAS  PubMed  Google Scholar 

  • Praticò D (2008) Evidence of oxidative stress in Alzheimer’s disease brain and antioxidant therapy: lights and shadows. Ann N Y Acad Sci 1147:70–78

    Article  PubMed  Google Scholar 

  • Porta F, Roato I, Mussa A et al (2008) Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria. J Inherit Metab Dis, epub ahead of print

  • Rake JP, Visser G, Huismans D et al (2003) Bone mineral density in children, adolescents and adults with glycogen storage disease type Ia: a cross-sectional and longitudinal study. J Inherit Metab Dis 26:371–384

    Article  CAS  PubMed  Google Scholar 

  • Riva E, Agostoni C, Biasucci G et al (1996) Early breastfeeding is linked to higher intelligence quotient scores in dietary treated phenylketonuric children. Acta Paediatr 85:56–58

    Article  CAS  PubMed  Google Scholar 

  • Rohr FJ, Munier AW, Levy HL (2001) Acceptability of a new modular protein substitute for the dietary treatment of phenylketonuria. J Inherit Metab Dis 24:623–630

    Article  CAS  PubMed  Google Scholar 

  • Rutherford P, Poustie VJ (2005) Protein substitute for children and adults with phenylketonuria. Cochrane Database Syst Rev 4:CD004731

    PubMed  Google Scholar 

  • Schönau E, Schwahn B, Rauch F (2002) The muscle-bone relationship: methods and management—perspectives in glycogen storage disease. Eur J Pediatr 161:S50–S52

    PubMed  Google Scholar 

  • Schulpis KH, Tsakiris S, Karikas GA, Moukas M, Behrakis P (2003) Effect of diet on plasma total antioxidant status in phenylketonuric patients. Eur J Clin Nutr 57:383–387

    Article  CAS  PubMed  Google Scholar 

  • Schulpis KH, Karakonstantakis T, Bartzeliotou A, Karikas GA, Papassotiriou I (2004) The association of serum lipids, lipoproteins and apolipoproteins with selected trace elements and minerals in phenylketonuric patients on diet. Clin Nutr 23:401–407

    Article  CAS  PubMed  Google Scholar 

  • Schulpis KH, Tsakiris S, Traeger-Synodinos J, Papassotiriou I (2005) Low total antioxidant status is implicated with high 8-hydroxy-2-deoxyguanosine serum concentrations in phenylketonuria. Clin Biochem 38:239–242

    Article  CAS  PubMed  Google Scholar 

  • Schwahn B, Mokov E, Scheidhauer K, Lettgen B, Schönau E (1998) Decreased trabecular bone mineral density in patients with phenylketonuria measured by peripheral quantitative computed tomography. Acta Paediatr 87:61–63

    Article  CAS  PubMed  Google Scholar 

  • Schwahn B, Rauch F, Wendel U, Schönau E (2002) Low bone mass in glycogen storage disease type 1 is associated with reduced muscle force and poor metabolic control. J Pediatr 141:350–356

    Article  PubMed  Google Scholar 

  • Sirtori LR, Dutra-Filho CS, Fitarelli D et al (2005) Oxidative stress in patients with phenylketonuria. Biochim Biophys Acta 1740:68–73

    CAS  PubMed  Google Scholar 

  • Sitta A, Barschak AG, Deon M et al (2006) Investigation of oxidative stress parameters in treated phenylketonuric patients. Metab Brain Dis 21:287–296

    Article  CAS  PubMed  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

    PubMed  Google Scholar 

  • van Rijn M, Bekhof J, Dijkstra T, Smit PG, Moddermam P, van Spronsen FJ (2003) A different approach to breast-feeding of the infant with phenylketonuria. Eur J Pediatr 162:323–326

    PubMed  Google Scholar 

  • Verduci E, Agostoni C, Biondi ML, Radaelli G, Giovannini M, Riva E (2004) Apolipoprotein B gene polymorphism and plasma lipid levels in phenylketonuric children. Prostaglandins Leukot Essent Fatty Acids 71:117–120

    Article  CAS  PubMed  Google Scholar 

  • Wajner M, Latini A, Wyse AT, Dutra-Filho CS (2004) The role of oxidative damage in the neuropathology of organic acidurias: insights from animal studies. J Inherit Metab Dis 27:427–448

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors take full responsibility for the content of this meeting report but thank Caudex Medical (supported by Serono Symposia International Foundation) for their assistance in editing this report and collating the comments of the authors and any other named contributors.

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Authors and Affiliations

  1. Centre de référence des maladies héréditaires du métabolisme de Nancy, INSERM U 954, Hôpital d’Enfants, CHU Brabois, Allée du Morvan, Vandoeuvre les Nancy, 54500, France

    François Feillet

  2. Department of Maternal and Pediatric Sciences, Fondazione IRCCS Cà Granda – Ospedale Maggiore Policlinico, University of Milan, Via della Commenda, 9, I-20122, Milano, Italy

    Carlo Agostoni

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  1. François Feillet
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  2. Carlo Agostoni
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Correspondence to François Feillet.

Additional information

Communicated by: Nenad Blau

Competing interest: None declared.

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Feillet, F., Agostoni, C. Nutritional issues in treating phenylketonuria. J Inherit Metab Dis 33, 659–664 (2010). https://doi.org/10.1007/s10545-010-9043-4

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