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Adjusting diet with sapropterin in phenylketonuria: what factors should be considered?

  • Anita MacDonald (a1), Kirsten Ahring (a2), Katharina Dokoupil (a3), Hulya Gokmen-Ozel (a4), Anna Maria Lammardo (a5), Kristina Motzfeldt (a6), Martine Robert (a7), Júlio César Rocha (a8), Margreet van Rijn (a9) and Amaya Bélanger-Quintana (a10)...
Abstract

The usual treatment for phenylketonuria (PKU) is a phenylalanine-restricted diet. Following this diet is challenging, and long-term adherence (and hence metabolic control) is commonly poor. Patients with PKU (usually, but not exclusively, with a relatively mild form of the disorder) who are responsive to treatment with pharmacological doses of tetrahydrobiopterin (BH4) have either lower concentrations of blood phenylalanine or improved dietary phenylalanine tolerance. The availability of a registered formulation of BH4 (sapropterin dihydrochloride, Kuvan®) has raised many practical issues and new questions in the dietary management of these patients. Initially, patients and carers must understand clearly the likely benefits (and limitations) of sapropterin therapy. A minority of patients who respond to sapropterin are able to discontinue the phenylalanine-restricted diet completely, while others are able to relax the diet to some extent. Care is required when altering the phenylalanine-restricted diet, as this may have unintended nutritional consequences and must be undertaken with caution. New clinical protocols are required for managing any dietary change while maintaining control of blood phenylalanine, ensuring adequate nutrition and preventing nutritional deficiencies, overweight or obesity. An accurate initial evaluation of pre-sapropterin phenylalanine tolerance is essential, and the desired outcome from treatment with sapropterin (e.g. reduction in blood phenylalanine or relaxation in diet) must also be understood by the patient and carers from the outset. Continuing education and support will be required thereafter, with further adjustment of diet and sapropterin dosage as a young patient grows.

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Corresponding author
*Corresponding author: A. MacDonald, fax +44 121 333 8021, email anita.macdonald@bch.nhs.uk
References
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1 Levy HL, Milanowski A, Chakrapani A, et al. , (2007) Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study. Lancet 370, 504510.
2 Trefz FK, Burton B, Longo N, et al. , (2009) Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in children with phenylketonuria: a phase III, randomized, double-blind, placebo-controlled study. J Pediatr 154, 700707.
3 Burton BK, Grange DK, Milanowski A, et al. (2007) The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study. J Inherit Metab Dis 30, 700707.
4 Bóveda MD, Couce ML, Castiñeiras DE, et al. (2007) The tetrahydrobiopterin loading test in 36 patients with hyperphenylalaninaemia: evaluation of response and subsequent treatment. J Inherit Metab Dis 30, 812.
5 Blau N, Belanger-Quintana A, Demirkol M, et al. (2009) Optimizing the use of sapropterin (BH(4)) in the management of phenylketonuria. Mol Genet Metab 96, 158163.
6 Feillet F, van Spronsen FJ, MacDonald A, et al. (2010) Challenges and pitfalls in the management of phenylketonuria. Pediatrics 126, 333341.
7 Trefz FK, Scheible D, Frauendienst-Egger G, et al. (2005) Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin. Mol Genet Metab 86, Suppl. 1, S75S80.
8 Burlina A & Blau N (2009) Effect of BH(4) supplementation on phenylalanine tolerance. J Inherit Metab Dis 32, 4045.
9 Fiege B, Bonafé L, Ballhausen D, et al. (2005) Extended tetrahydrobiopterin loading test in the diagnosis of cofactor-responsive phenylketonuria: a pilot study. Mol Genet Metab 86, Suppl. 1, S91S95.
10 Nielsen JB, Nielsen KE & Güttler F (2010) Tetrahydrobiopterin responsiveness after extended loading test of 12 Danish PKU patients with the Y414C mutation. J Inherit Metab Dis 33, 916.
11 Muntau AC, Röschinger W, Habich M, et al. (2002) Tretrahydrobiopterin as an alternative treatment for mild phenylketonuria. N Engl J Med 347, 21222132.
12 Baldellou Vázquez A, Salazar García-Blanco MI, Ruiz-Echarri Zalaya MP, et al. (2006) Tetrahydrobiopterin therapy for hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. When and how? (article in Spanish). An Pediatr (Barc) 64, 146152.
13 Trefz FK & Blau N (2003) Potential role of tetrahydrobiopterin in the treatment of maternal phenylketonuria. Pediatrics 112, 15661569.
14 Koch R (2008) Maternal phenylketonuria and tetrahydrobiopterin. Pediatrics 122, 13671368.
15 Cunningham A, Pridijian G, Smith J, et al. (2009) PKU treatment with tetrhydrobiopterin (sapropterin) during pregnancy. Mol Genet Metab 98, 24 (abstract 187).
16 Rocha JC, Almeida MF, Carmona C, et al. (2010) The use of prealbumin concentration as a biomarker of nutritional status in treated phenylketonuric patients. Ann Nutr Metab 56, 207211.
17 Acosta PB (2010) Evaluation of nutrition status. In Nutrition Management of Patients with Inherited Metabolic Disorders, pp. 6798 [Acosta PB, editor]. Sudbury: Jones and Bartlett.
18 Mitchell JJ, Wilcken B, Alexander I, et al. (2005) Tetrahydrobiopterin-responsive phenylketonuria: the New South Wales experience. Mol Genet Metab 86, Suppl. 1, S81S85.
19 Blau N, van Spronsen FJ & Levy HL (2010) Phenylketonuria. Lancet 376, 14171427.
20 Desviat LR, Pérez B, Bèlanger-Quintana A, et al. (2004) Tetrahydrobiopterin responsiveness: results of the BH4 loading test in 31 Spanish PKU patients and correlation with their genotype. Mol Genet Metab 83, 157162.
21 Shintaku H, Kure S, Ohura T, et al. (2004) Long-term treatment and diagnosis of tetrahydrobiopterin-responsive hyperphenylalaninemia with a mutant phenylalanine hydroxylase gene. Pediatr Res 55, 425430.
22 Somaraju UR & Merrin M (2010) Sapropterin dihydrochloride for phenylketonuria. The Cochrane Database of Systematic Reviews, issue 6, CD008005.
23 Bélanger-Quintana A, García MJ, Castro M, et al. (2005) Spanish BH4-responsive phenylalanine hydroxylase-deficient patients: evolution of seven patients on long-term treatment with tetrahydrobiopterin. Mol Genet Metab 86, Suppl. 1, S61S66.
24 Hennermann JB, Bührer C, Blau N, et al. (2005) Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria. Mol Genet Metab 86, Suppl. 1, S86S90.
25 Lambruschini N, Pérez-Dueñas B, Vilaseca MA, et al. (2005) Clinical and nutritional evaluation of phenylketonuric patients on tetrahydrobiopterin monotherapy. Mol Genet Metab 86, S54S60.
26 Singh R, Jurecki E & Rohr F (2008) Recommendations for personalized dietary adjustments based on patient response of tetrahydrobiopterin in phenylketonuria. Top Clin Nutr 23, 149157.
27 Singh RH, Quirk ME, Douglas TD, et al. (2010) BH(4) therapy impacts the nutrition status and intake in children with phenylketonuria: 2-year follow-up. J Inherit Metab Dis 33, 689695.
28 WHO/FAO/UNU (2010) Protein and Amino Acid Requirements in Human Nutrition. Report of a Joint WHO/FAO/UNU Expert Consultation WHO Technical Report Series. no. 935. http://whqlibdoc.who.int/trs/WHO_TRS_935_eng.pdf (accessed March 2010).
29 Kindt E, Motzfeldt K & Halvorsen S (1984) Is phenylalanine requirement in infants and children related to protein intake? Br J Nutr 51, 435442.
30 Acosta PB & Yannicelli S (1994) Protein intake affects phenylalanine requirements and growth of infants with phenylketonuria. Acta Paediatr Suppl 407, 6667.
31 MacDonald A, Daly A & Davies P (2004) Protein substitutes for PKU: what's new? J Inherit Metab Dis 27, 363371.
32 van Spronsen FJ, Hoeksma M & Reijngoud DJ (2009) Brain dysfunction in phenylketonuria: is phenylalanine toxicity the only possible cause? J Inherit Metab Dis 32, 4651.
33 vanSpronsen FJ, deGroot MJ, Hoeksma M, et al. (2010) Large neutral amino acids in the treatment of PKU: from theory to practice. J Inherit Metab Dis 33, 671676.
34 Humphrey M, Francis I, Upton H, et al. (2009) Effect of BH4 on phe/tyr ratio and fluctuations in phe levels in BH4 responsiveness PKU patients. Mol Genet Metab 98, 25 (abstract 194).
35 Feillet F & Agostoni C (2010) Nutritional issues in treating phenylketonuria. J Inherit Metab Dis 33, 659664.
36 Scaglioni S, Verduci E, Fiori L, et al. (2004) Body mass index rebound and overweight at 8 years of age in hyperphenylalaninaemic children. Acta Paediatr 93, 15961600.
37 Lee P, Treacy EP, Crombez E, et al. (2008) Safety and efficacy of 22 weeks of treatment with sapropterin dihydrochloride in patients with phenylketonuria. Am J Med Genet A 146A, 28512859.
38 Fernhoff PM, Burton BK & Nowacka M (2009) PKU-008: A Long-term, Open-label Study of Sapropterin Dihydrochloride (Kuvan®) in PKU subjects Abstract no. 190 presented at the 2009 Meeting of the American College of Medical Genetics. http://submissions.miracd.com/acmg/ContentInfo.aspx?conID = 1135 (accessed February 2010).
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
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