British Journal of Nutrition

Review Article

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

Anita MacDonalda1 c1, Kirsten Ahringa2, Katharina Dokoupila3, Hulya Gokmen-Ozela4, Anna Maria Lammardoa5, Kristina Motzfeldta6, Martine Roberta7, Júlio César Rochaa8, Margreet van Rijna9 and Amaya Bélanger-Quintanaa10

a1 The Children's Hospital, Birmingham, West Midlands B4 6NH, UK

a2 Department of PKU, Kennedy Centre, Glostrup, Denmark

a3 Department of Metabolism and Nutrition, Dr von Hauner Children's Hospital, University of Munich, Munich, Germany

a4 Department of Nutrition and Dietetics, Hacettepe University, Ankara, Turkey

a5 Department of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy

a6 Women and Children's Division, Department of Pediatrics, Section for Specialized Medicine and Unit for Newborn Screening, Oslo University Hospital Rikshospitalet, Oslo, Norway

a7 Nutrition and Metabolism Unit, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium

a8 Centro de Genética Médica Jacinto de Magalhães, Instituto Nacional de Saúde, Porto, Portugal

a9 Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Centre, Groningen, The Netherlands

a10 Unidad Enfermendades Metabolicas, Servicio de Pediatria Hospital Ramon y Cajal, Madrid, Spain


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.

(Received July 14 2010)

(Revised December 15 2010)

(Accepted January 17 2011)

(Online publication April 05 2011)


c1 Corresponding author: A. MacDonald, fax +44 121 333 8021, email


Abbreviations: BH4, tetrahydrobiopterin; PAH, phenylalanine hydroxylase; PKU, phenylketonuria