Longitudinal Dietary Intake Data in Patients with Phenylketonuria from Europe: The Impact of Age and Phenylketonuria Severity
Alex Pinto,
Kirsten Ahring,
Manuela Ferreira Almeida,
Catherine Ashmore,
Amaya Bélanger-Quintana,
Alberto Burlina,
Turgay Coşkun,
Anne Daly,
Esther van Dam,
Ali Dursun,
Sharon Evans,
François Feillet,
Maria Giżewska,
Hulya Gökmen-Özel,
Mary Hickson,
Yteke Hoekstra,
Fatma Ilgaz,
Richard Jackson,
Alicja Leśniak,
Christian Loro,
Katarzyna Malicka,
Michał Patalan,
Júlio César Rocha,
Serap Sivri,
Iris Rodenburg,
Francjan van Spronsen,
Kamilla Strączek,
Ayşegül Tokatli,
Anita MacDonald
Affiliations
Alex Pinto
Birmingham Children’s Hospital, Birmingham B4 6NH, UK
Kirsten Ahring
Department of PKU, Copenhagen University Hospital, 2100 København, Denmark
Manuela Ferreira Almeida
Centro de Genética Médica, Unidade Local de Saúde de Santo António, E.P.E. (ULSSA), 4099-028 Porto, Portugal
Catherine Ashmore
Birmingham Children’s Hospital, Birmingham B4 6NH, UK
Amaya Bélanger-Quintana
Unidad de Enfermedades Metabólicas Congénitas, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
Alberto Burlina
Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, Department of Women’s and Children’s Health, University Hospital, 35128 Padova, Italy
Turgay Coşkun
Department of Pediatric Metabolism and Nutrition, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey
Anne Daly
Birmingham Children’s Hospital, Birmingham B4 6NH, UK
Esther van Dam
Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Ali Dursun
Department of Pediatric Metabolism and Nutrition, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey
Sharon Evans
Birmingham Children’s Hospital, Birmingham B4 6NH, UK
François Feillet
Department of Paediatrics, Reference Center for Inborn Errors of Metabolism, Hôpital d’Enfants Brabois, CHU Nancy, 54500 Vandoeuvre les Nancy, France
Maria Giżewska
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases, and Cardiology of the Developmental Age, Pomeranian Medical University, 70-204 Szczecin, Poland
Hulya Gökmen-Özel
Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Ankara, Turkey
Mary Hickson
School of Health Professions, Faculty of Health, University of Plymouth, Plymouth PL4 6AB, UK
Yteke Hoekstra
Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Fatma Ilgaz
Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Ankara, Turkey
Richard Jackson
Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool L69 3GL, UK
Alicja Leśniak
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases, and Cardiology of the Developmental Age, Pomeranian Medical University, 70-204 Szczecin, Poland
Christian Loro
Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, Department of Women’s and Children’s Health, University Hospital, 35128 Padova, Italy
Katarzyna Malicka
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases, and Cardiology of the Developmental Age, Pomeranian Medical University, 70-204 Szczecin, Poland
Michał Patalan
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases, and Cardiology of the Developmental Age, Pomeranian Medical University, 70-204 Szczecin, Poland
Júlio César Rocha
Nutrition and Metabolism, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
Serap Sivri
Department of Pediatric Metabolism and Nutrition, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey
Iris Rodenburg
Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Francjan van Spronsen
Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands
Kamilla Strączek
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases, and Cardiology of the Developmental Age, Pomeranian Medical University, 70-204 Szczecin, Poland
Ayşegül Tokatli
Department of Pediatric Metabolism and Nutrition, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey
Anita MacDonald
Birmingham Children’s Hospital, Birmingham B4 6NH, UK
In phenylketonuria (PKU), natural protein intake is thought to increase with age, particularly during childhood and adolescence. Longitudinal dietary intake data are scarce and lifelong phenylalanine tolerance remains unknown. Nine centres managing PKU in Europe and Turkey participated in a retrospective study. Data were collected from dietetic records between 2012 and 2018 on phenylalanine (Phe), natural protein, and protein substitute intake. A total of 1323 patients (age range: 1–57 y; 51% male) participated. Dietary intake data were available on 1163 (88%) patients. Patient numbers ranged from 59 to 320 in each centre. A total of 625 (47%) had classical PKU (cPKU), n = 357 (27%) had mild PKU (mPKU), n = 325 (25%) had hyperphenylalaninemia (HPA), and n = 16 (1%) were unknown. The mean percentage of blood Phe levels within target ranged from 65 ± 54% to 88 ± 49%. When intake was expressed as g/day, the mean Phe/natural protein and protein equivalent from protein substitute gradually increased during childhood, reaching a peak in adolescence, and then remained consistent during adulthood. When intake was expressed per kg body weight (g/kg/day), there was a decline in Phe/natural protein, protein equivalent from protein substitute, and total protein with increasing age. Overall, the mean daily intake (kg/day) was as follows: Phe, 904 mg ± 761 (22 ± 23 mg/kg/day), natural protein 19 g ± 16 (0.5 g/kg/day ± 0.5), protein equivalent from protein substitute 39 g ± 22 (1.1 g/kg/day ± 0.6), and total protein 59 g ± 21 (1.7 g/kg/day ± 0.6). Natural protein tolerance was similar between males and females. Patients with mPKU tolerated around 50% less Phe/natural protein than HPA, but 50% more than cPKU. Higher intakes of natural protein were observed in Southern Europe, with a higher prevalence of HPA and mPKU compared with patients from Northern European centres. Natural protein intake doubled with sapropterin usage. In sapropterin-responsive patients, 31% no longer used protein substitutes. Close monitoring and optimisation of protein intake prescriptions are needed, along with future guidelines specifically for different age groups and severities.