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Fatty acid profile in patients with phenylketonuria and its relationship with bone mineral density

  • Research Report
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Background

Patients with phenylketonuria (PKU) undergo a restrictive vegan-like diet, with almost total absence of n-3 fatty acids, which have been proposed as potential contributors to bone formation in the healthy population. The PKU diet might lead these patients to bone mass loss and, consequently, to the development of osteopenia/osteoporosis. Therefore, we proposed to analyze their plasma fatty acid profile status and its relationship with bone health.

Methods

We recruited 47 PKU patients for this cross-sectional study and divided the cohort into three age groups (6–10 years, 11–18 years, 19–42 years). We measured their plasma fatty acid profile and bone mineral density (BMD) (both at the femoral neck and the lumbar spine). Seventy-seven healthy controls also participated as reference values of plasma fatty acids.

Results

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and total n-3 fatty acids were significantly diminished in PKU patients compared with healthy controls. DHA, EPA, and total n-3 fatty acids were also positively associated with bone mineral density (r = 0.83, p = 0.010; r = 0.57, p = 0.006; r = 0.73, p = 0.040, respectively). There was no association between phenylalanine (Phe), Index of Dietary Control (IDC), calcium, 25-hydroxivitamin D concentrations, daily calcium intake, and BMD.

Conclusion

Our results suggest a possible influence of essential fatty acids over BMD in PKU patients. The lack of essential n-3 fatty acids intake in the PKU diet might affect bone mineralization. Further clinical trials are needed to confirm the effect of the n-3 essential fatty acids on bone accrual in a cohort of PKU patients.

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Abbreviations

BMD:

bone mineral density

BMI:

body mass index

DHA:

docosahexaenoic acid

EPA:

eicosapentaenoic acid

LC-PUFA:

long-chain polyunsaturated fatty acid

MUFA:

monounsaturated fatty acid

PKU:

phenylketonuria

PUFA:

polyunsaturated fatty acid

RDA:

recommended dietary allowances

SD:

standard deviation

SFA:

saturated fatty acid

References

  • Acosta PB, Yannicelli S, Singh R, Eisas LJ 2nd, Kennedy MJ, Bernstein L, Rohr F, Trahms C, Koch R, Breck J (2001) Intake and blood levels of fatty acids in treated patients with phenylketonuria. J Pediatr Gastroenterol Nutr 33:253–259

    Article  PubMed  CAS  Google Scholar 

  • Agostoni C, Riva E, Biasucci G, Luotti D, Bruzzese MG, Marangoni F, Giovannini M (1995) The effects of n-3 and n-6 polyunsaturated fatty acids on plasma lipids and fatty acids of treated phenylketonuric children. Prostaglandins Leukot Essent Fatty Acids 53:401–404

    Article  PubMed  CAS  Google Scholar 

  • Allen JR, Humphries IR, Waters DL et al (1994) Decreased bone mineral density in children with phenylketonuria. Am J Clin Nutr 59:419–422

    PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Campistol Plana J, Lambruschini Ferri N, Vilaseca Buscá MA, Pérez-Dueñas B, Fusté Rich E, Gómez López L (2006) Hiperfenilalaninemia. In: Sanjurjo P, Baldellou A (eds) Diagnóstico y tratamiento de las enfermedades metabólicas hereditarias, 2nd edn. Ergon, Madrid, pp 305–319

    Google Scholar 

  • Carson DJ, Greeves LG, Sweeney LE, Crone MD (1990) Osteopenia and phenylketonuria. Pediatr Radiol 20:598–599

    Article  PubMed  CAS  Google Scholar 

  • Claassen N, Coetzer H, Steinmann CM, Kruger MC (1995a) The effect of different n-6/n-3 essential fatty acid ratios on calcium balance and bone in rats. Prostaglandins Leukot Essent Fatty Acids 53:13–19

    Article  CAS  Google Scholar 

  • Claassen N, Potgieter HC, Seppa M et al (1995b) Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status in young male rats: effects on free urinary collagen crosslinks, total urinary hydroxyproline, and bone calcium content. Bone 16:385S–392S

    Article  CAS  Google Scholar 

  • Dhondt JL, Largillière C, Moreno L, Farriaux JP (1995) Physical growth in patients with phenylketonuria. J Inherit Metab Dis 18:135–137

    Article  PubMed  CAS  Google Scholar 

  • Dobbelaere D, Michaud L, Debrabander A et al (2003) Evaluation of nutritional status and pathophysiology of growth retardation in patients with phenylketonuria. J Inherit Metab Dis 26:1–11

    Article  PubMed  CAS  Google Scholar 

  • Eriksson S, Mellström D, Strandvik B (2009) Fatty acid pattern in serum is associated with bone mineralisation in healthy 8-year-old children. Br J Nutr 102:407–412

    Article  PubMed  CAS  Google Scholar 

  • Feillet F, Agostoni C (2010) Nutritional issues in treating phenylketonuria. J Inherit Metab Dis [Epub ahead of print]

  • Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Haag M, Magada ON, Claassen N, Böhmer LH, Kruger MC (2003) Omega-3 fatty acids modulate ATPases involved in duodenal Ca absorption. Prostaglandins Leukot Essent Fatty Acids 68:423–429

    Article  PubMed  CAS  Google Scholar 

  • Hernández M, Sánchez E, Sobradillo B (2000) Curvas y tablas de crecimiento. In: Argente J, Carrascosa A, Gracia R, Rodríguez F (eds) Tratado de endocrinología pediátrica y de la adolescencia, 2nd edn. Ediciones Doyma, Barcelona, pp 1441–1499

    Google Scholar 

  • Hillman L, Schlotzhauer C, Lee D et al (1996) Decreased bone mineralization in children with phenylketonuria under treatment. Eur J Pediatr 155:S148–152

    Article  PubMed  Google Scholar 

  • Högström M, Nordström P, Nordström A (2007) n-3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 Study. Am J Clin Nutr 85:803–807

    PubMed  Google Scholar 

  • Innis SM (1992) Plasma and red blood cell fatty acid values as indexes of essential fatty acids in the developing organs of infants fed with milk or formulas. J Pediatr 120:S78-S86

    Article  PubMed  CAS  Google Scholar 

  • Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381

    Article  PubMed  CAS  Google Scholar 

  • Koletzko B, Beblo S, Demmelmair H, Müller-Felber W, Hanebutt FL (2009a) Does dietary DHA improve neural function in children? Observations in phenylketonuria. Prostaglandins Leukot Essent Fatty Acids 81:159–164

    Article  CAS  Google Scholar 

  • Koletzko B, Beblo S, Demmelmair H, Hanebutt FL (2009b) Omega-3 LC-PUFA supply and neurological outcomes in children with phenylketonuria (PKU). J Pediatr Gastroenterol Nutr 48(Suppl 1):S2–7

    Article  CAS  Google Scholar 

  • Koletzko B, Sauerwald T, Demmelmair H, Herzog M, von Schenck U, Böhles H, Wendel U, Seidel J (2007) Dietary long-chain polyunsaturated fatty acid supplementation in infants with phenylketonuria: a randomized controlled trial. J Inherit Metab Dis 30:326-332

    Article  PubMed  CAS  Google Scholar 

  • Kruger MC, Horrobin DF (1997) Calcium metabolism, osteoporosis and essential fatty acids: a review. Prog Lipid Res 36:131–151

    Article  PubMed  CAS  Google Scholar 

  • Kruger MC, Schollum LM (2005) Is docosahexaenoic acid more effective than eicosapentaenoic acid for increasing calcium bioavailability? Prostaglandins Leukot Essent Fatty Acids 73:327–334

    Article  PubMed  CAS  Google Scholar 

  • Lavoie SM, Harding CO, Gillingham MB (2009) Normal fatty acid concentration in young children with phenylketonuria (PKU). Top Clin Nutr 24:333-340

    PubMed  Google Scholar 

  • Lepage G, Roy CC (1986) Direct transesterification of all classes of lipids in a one-step reaction. J Lipid Res 27:114–120

    PubMed  CAS  Google Scholar 

  • McMurry MP, Chan GM, Leonard CO, Ernst SL (1992) Bone mineral status in children with phenylketonuria–relationship to nutritional intake and phenylalanine control. Am J Clin Nutr 55:997–1004

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Pérez-Dueñas B, Cambra FJ, Vilaseca MA, Lambruschini N, Campistol J, Camacho JA (2002) New approach to osteopenia in phenylketonuric patients. Acta Paediatr 91:899–904

    Article  PubMed  Google Scholar 

  • 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 21:373–381

    Article  PubMed  Google Scholar 

  • Porta F, Roato I, Mussa A, Repici M, Gorassini E, Spada M, Ferracini R (2008) Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria. J Inherit Metab Dis [Epub ahead of print]

  • Przyrembel H, Bremer HJ (2000) Nutrition, physical growth, and bone density in treated phenylketonuria. Eur J Pediatr 159:S129–135

    Article  PubMed  CAS  Google Scholar 

  • Rauch F, Plotkin H, DiMeglio L (2008) Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2007 Pediatric Official Positions. J Clin Densitom 11:22–28

    Article  Google Scholar 

  • Sanjurjo P, Perteagudo L, Rodríguez Soriano J, Vilaseca A, Campistol J (1994) Polyunsaturated fatty acid status in patients with phenylketonuria. J Inherit Metab Dis 17:704–709

    Article  PubMed  CAS  Google Scholar 

  • Schaefer F, Burgard P, Batzler U (1994) Growth and skeletal maturation in children with phenylketonuria. Acta Paediatr 83:534–541

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Skeaff CM, Hodson L, McKenzie JE (2006) Dietary-induced changes in fatty acid composition of human plasma, platelet, and erythrocyte lipids follow a similar time course. J Nutr 136:565–569

    PubMed  CAS  Google Scholar 

  • van Gool CJ, van Houwelingen AC, Hornstra G (2000) The essential fatty acid status in phenylketonuria patients under treatment. J Nutr Biochem 11:543–547

    Article  PubMed  Google Scholar 

  • Verkerk PH, van Spronsen FJ, Smit GP, Sengers RC (1994) Impaired prenatal and postnatal growth in Dutch patients with phenylketonuria. The National PKU Steering Committee. Arch Dis Child 71:114–118

    Article  PubMed  CAS  Google Scholar 

  • Vilaseca MA, Lambruschini N, Gómez-López L, Gutiérrez A, Moreno J, Tondo M, Artuch R, Campistol J (2010) Long-chain polyunsaturated fatty acid status in phenylketonuric patients treated with tetrahydrobiopterin. Clin Biochem 43:411–415

    Article  PubMed  CAS  Google Scholar 

  • Watkins BA, Li Y, Lippman HE, Feng S (2003) Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins Leukot Essent Fatty Acids 68:387–398

    Article  PubMed  CAS  Google Scholar 

  • Weiler HA, Fitzpatrick-Wong SC (2002) Modulation of essential (n-6):(n-3) fatty acid ratios alters fatty acid status but not bone mass in piglets. J Nutr 132:2667–2672

    PubMed  CAS  Google Scholar 

  • Weiss LA, Barrett-Connor E, von Mühlen D (2005) Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study. Am J Clin Nutr 81:934–938

    PubMed  CAS  Google Scholar 

  • Zeman J, Bayer M, Stepán J (1999) Bone mineral density in patients with phenylketonuria. Acta Paediatr 88:1348–1351

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We acknowledge support from O+IKER (Basque Institute for Healthcare Research, Basque Foundation for Healthcare Innovation and Research), Mutua Madrileña Foundation (MUTUAM09/013), and Red SAMID (Red de Salud Materno-Infantil y del Desarrollo RD08/0072/0036 – Spanish Research Network for Maternal and Child Health and Development).

Funding

This study was funded by Mutua Madrileña Foundation (MUTUAM09/013). The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsor.

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Authors and Affiliations

  1. Division of Metabolism, Department of Paediatrics, Cruces Hospital, Plaza de Cruces s/n, 48903, Barakaldo, Vizcaya, Spain

    Sergio Lage, Fernando Andrade, José Ángel Prieto, María Legarda, Pablo Sanjurjo & Luis Jose Aldámiz-Echevarría

  2. Department of Paediatrics, Virgen del Rocío Teaching Hospital, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain

    María Bueno

  3. Faculty of Medicine and Surgery, Basque Country University, Barrio de Sarriena s/n, 48940, Leioa, Vizcaya, Spain

    Pablo Sanjurjo

  4. Metabolic Pathologies Laboratory, Virgen del Rocío Teaching Hospital, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain

    Carmen Delgado

Authors
  1. Sergio Lage
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  2. María Bueno
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  3. Fernando Andrade
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  8. Luis Jose Aldámiz-Echevarría
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Corresponding author

Correspondence to Luis Jose Aldámiz-Echevarría.

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Communicated by: John H. Walter

Competing interest: None declared.

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Lage, S., Bueno, M., Andrade, F. et al. Fatty acid profile in patients with phenylketonuria and its relationship with bone mineral density. J Inherit Metab Dis 33 (Suppl 3), 363–371 (2010). https://doi.org/10.1007/s10545-010-9189-0

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  • DOI: https://doi.org/10.1007/s10545-010-9189-0

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