Advances in Phenylketonuria (PKU) Nutrition and Diet Research (2nd Edition)
A project collection of Nutrients (ISSN 2072-6643). This project collection belongs to the section "Nutritional Epidemiology".
Papers displayed on this page all arise from the same project. Editorial decisions were made independently of project staff and handled by the Editor-in-Chief or qualified Editorial Board members.
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Editors
Prof. Dr. Júlio César Rocha
Prof. Dr. Júlio César Rocha
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1. NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal
2. Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
3. CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal
Interests: inherited metabolic diseases; nutrition; dietetics; metabolism; nutritional status
Special Issues, Collections and Topics in MDPI journals
Project Overview
Dear Colleagues,
It has been 70 years since the introduction of the first successful dietary therapy for a child with phenylketonuria (PKU) at Birmingham’s Children's Hospital, UK. Even though the initial synthetic phenylalanine (Phe) restricted diet was unpalatable and very abnormal compared to a regular diet, its impact on improving blood Phe metabolic control was clear. It is remarkable that after so many decades, the principles of nutritional management rely on the same approach, particularly in patients who are not candidates for alternative pharmacological therapies. Advancing and comprehensive knowledge of molecular genetics indicates that PKU is a condition that can be managed by a personalized therapeutic approach using pharmaceutical treatment options usually in combination with dietary treatments. This has introduced many challenging questions about the real impact of new therapies on dietary patterns, food choices, nutritional status and the development of co-morbidities in patients with PKU. Several areas of dietary management remain unclear or unchallenged. We underline the importance of health professionals collecting routine systematic data in patients with PKU to fully understand all aspects of treatment impact instead of spending countless hours debating unknown and controversial aspects of care. Meta-analysis and systematic reviews are very good opportunities to methodologically summarise current scientific evidence, helping to guide clinical practice and open new avenues for targeted research. We warmly challenge and invite our colleagues to engrain research practices into all aspects of training and clinical activities. Only in this way can we gain robust data that will improve clinical treatment practices and patient care. Although we do not close the door to experimental research, we do expect this Special Issue to specifically promote all current Advances in Phenylketonuria (PKU) Nutrition and Dietetic Research.
Prof. Dr. Júlio César Rocha
Prof. Dr. Anita MacDonald
Guest Editors
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Keywords
- phenylketonuria
- nutrition
- metabolism
- nutritional status
- diet
- body composition
- dietetics
- nutrition psychology
- feeding development
- childhood nutrition
- disordered eating
Published Papers (8 papers)
Open AccessArticle
Nutritional Counseling Promotes Adherence to the Mediterranean Diet and Healthy Eating in Italian Patients Affected by Phenylketonuria and Treated with Pegvaliase
by
Michele Stecchi, Alice Rossi, Michelle Santoni, Francesca Bandini and Lucia Brodosi
Viewed by 817
Abstract
Background/Objectives: Pegvaliase, a subcutaneous therapy to treat phenylketonuria (PKU), has allowed these patients to maintain adequate phenylalanine (Phe) blood values without following a Phe-controlled diet; this brings up the challenge of promoting healthy eating while moving away from prescription diets. In our center,
[...] Read more.
Background/Objectives: Pegvaliase, a subcutaneous therapy to treat phenylketonuria (PKU), has allowed these patients to maintain adequate phenylalanine (Phe) blood values without following a Phe-controlled diet; this brings up the challenge of promoting healthy eating while moving away from prescription diets. In our center, every patient treated with Pegvaliase undergoes routine nutritional counseling aimed at promoting adherence to the Mediterranean diet (MedDiet) during regular inpatient visits. This study aims to assess adherence to MedDiet and the adequacy of the diets of patients treated with Pegvaliase regarding micro- and macronutrients. Methods: Seven patients on chronic therapy with Pegvaliase underwent a dietetic evaluation to assess the composition of their diets in terms of micro- and macronutrients; they were also administered the Mediterranean Diet Score (MDS) questionnaire. Subcategories from MDS were extracted to evaluate the consumption of foods typically included (vegetables, olive oil, etc.) and typically excluded (red meat, etc.) in the MedDiet. To assess the adequacy of the diet, nutrient and energy levels were compared with guidelines for the Italian population. Results: MedDiet adherence in our sample was comparable to the general population; in terms of macronutrients, good adherence to the recommendations was observed, with every one of them met except for excessive simple sugar consumption. Micronutrient dietary intake was inadequate for zinc, iron, selenium, folate, thiamine, and riboflavin. Conclusions: While more work is necessary to help patients treated with Pegvaliase to progress toward healthy eating, our study suggests that nutritional counseling routinely performed during inpatient visits, typically twice a year, effectively promotes healthier eating habits than those observed in the general population.
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Open AccessReview
Glycomacropeptide-Based Protein Substitutes for Children with Phenylketonuria in Italy: A Nutritional Comparison
by
Martina Tosi, Laura Fiori, Veronica Maria Tagi, Mirko Gambino, Chiara Montanari, Alessandra Bosetti, Gianvincenzo Zuccotti and Elvira Verduci
Viewed by 1540
Abstract
Advancements in food science technology have allowed the development of new products for the therapeutic management of inherited metabolic diseases such as phenylketonuria (PKU). Glycomacropeptide (GMP), a peptide derived from casein, is naturally low in phenylalanine (Phe) and, thus, adequate for protein substitutes
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Advancements in food science technology have allowed the development of new products for the therapeutic management of inherited metabolic diseases such as phenylketonuria (PKU). Glycomacropeptide (GMP), a peptide derived from casein, is naturally low in phenylalanine (Phe) and, thus, adequate for protein substitutes (PSs) for the management of PKU in children. This review aims primarily to analyse the differences in the nutritional composition of GMP-based protein substitutes in different formulations (ready to drink, powdered, and bars), and secondarily to assess the quality of these products, comparing their nutritional composition with that of standard amino acid (L-AA) mixtures. Thirty-five GMP-based PSs produced by six different companies were included in this review: twenty-one powdered PSs, eight ready to drink, and six bars. The analysis revealed great heterogeneity not only among the different formulations (powdered, ready to drink, and bars) but also within the same group, in terms of energy content and nutritional composition. GMP-based PSs were shown to have higher contents of sugars and saturated fatty acids compared to L-AA PSs, especially in ready-to-drink formulations and bars. The latter also provided the highest amounts of energy among the GMP-based products. This finding may be related to a higher risk of developing overweight and obesity. The greater palatability of these GMP-based PSs, combined with improved nutritional quality, could not only improve adherence to diet therapy but also reduce the incidence of obesity-related comorbidities in PKU.
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Open AccessOpinion
Intake Modalities of Amino Acid Supplements: A Real-World Data Collection from Phenylketonuria Patients
by
Albina Tummolo, Rosa Carella, Pasquale Carone, Giulia Paterno and Donatella De Giovanni
Cited by 1 | Viewed by 1281
Abstract
Background: To achieve a normal nutritional status, patients suffering from phenylketonuria (PKU) are typically prescribed amino acid (AA) supplements with low or no phenylalanine (Phe) content. Studies evaluating patient preferences regarding the intake modalities of AA supplements are limited. This study aimed to
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Background: To achieve a normal nutritional status, patients suffering from phenylketonuria (PKU) are typically prescribed amino acid (AA) supplements with low or no phenylalanine (Phe) content. Studies evaluating patient preferences regarding the intake modalities of AA supplements are limited. This study aimed to collect real-world data regarding prescription adherence and intake modalities of AA supplements reported by PKU patients while monitoring metabolic control. Methods: This cross-sectional study included 33 PKU patients (16 female and 17 male) with a mean age of 27.2 years. Questionnaires were provided to assess information on AA supplement intake, such as prescription adherence rate, frequency and timing of administration, supplement formulation, and combination with food or drinks. Plasma phenylalanine levels were monitored during the study period. Results: 51.5% (
n = 17) of patients reported to lay within an adherence range of 75–100%. The majority of patients consumed AA supplements twice daily, with breakfast (87.9%) and afternoon snacks (51.5%). Powder supplements were most commonly used (72.7%) and often combined with milk and/or fruit juices (45.4%). Conclusions: Despite the known concerns related to treatment compliance among PKU adolescents and adults, most of the study participants reported a high level of adherence to AA supplement prescription. The personalized dietary regimens followed by the patients included in the current study represent a treatment approach that might be worth trying in non-compliant patients.
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Open AccessReview
Are Phe-Free Protein Substitutes Available in Italy for Infants with PKU All the Same?
by
Elvira Verduci, Martina Tosi, Chiara Montanari, Mirko Gambino, Francesca Eletti, Alessandra Bosetti, Margherita Di Costanzo, Maria Teresa Carbone, Giacomo Biasucci, Laura Fiori and Gianvincenzo Zuccotti
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Abstract
Breastfeeding or standard infant formulas, alongside phenylalanine (Phe)-free protein substitutes, constitute the dietary management for infants with PKU to guarantee protein requirements are met in compliance with metabolic tolerance. This work aims to analyse the nutritional composition of Phe-free infant protein substitutes, in
[...] Read more.
Breastfeeding or standard infant formulas, alongside phenylalanine (Phe)-free protein substitutes, constitute the dietary management for infants with PKU to guarantee protein requirements are met in compliance with metabolic tolerance. This work aims to analyse the nutritional composition of Phe-free infant protein substitutes, in terms of macronutrients, micronutrients and functional components, available for PKU dietary management in Italy. A total of seven infant Phe-free protein substitutes were included in this review, six powder and one liquid. A second analysis was conducted to compare them to the composition of formulas intended for healthy infants, taking into consideration the Commission Delegated Regulation (EU) 2016/127 and Commission Delegated Regulation (EU) 2016/128 for micronutrients. The analysis revealed heterogeneity among protein substitutes suitable for infants with PKU. The energy and protein equivalents (P.Eq.) content are different; all of the substitutes contain docosahexaenoic acid (DHA) and arachidonic acid (ARA), while eicosapentaenoic acid (EPA), fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), human milk oligosaccharides (HMOs) and nucleotides are not present in all the substitutes. More attention should be paid to these infant products to ensure metabolic control of PKU, and also promote proper growth, cognitive neurodevelopment, favourable gut microbiota composition, and immune system health, while reducing the risk for non-communicable diseases (NCDs).
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Open AccessArticle
Adult PKU Clinics in the UK—Users’ Experiences and Perspectives
by
Fatma Ilgaz, Suzanne Ford, Michael F. O’Driscoll and Anita MacDonald
Cited by 5 | Viewed by 2408
Abstract
Adults with PKU require life-long management, and ideally, their care should be in a specialised adult metabolic clinic. Their outcomes and co-morbidities have received much attention, but data are lacking on their experience, satisfaction and expectations about the care they receive. This survey
[...] Read more.
Adults with PKU require life-long management, and ideally, their care should be in a specialised adult metabolic clinic. Their outcomes and co-morbidities have received much attention, but data are lacking on their experience, satisfaction and expectations about the care they receive. This survey reports the experiences and care adults with PKU receive from specialist metabolic clinics in the UK. The online survey developed by the UK NSPKU (National Society for Phenylketonuria), was placed on the NSPKU website from February 2021 to December 2022, and was completed by adults with PKU (≥18 years) or their carers/family members. Sixty-five adult PKU patients and 9 caregivers of adult patients completed the questionnaire (63% female in total). Only 32% of respondents were following a Phe-restricted diet with protein substitute intake as prescribed; the rest were partially adherent or not on dietary restrictions. Nineteen per cent (
n = 14/74) had not been reviewed in clinic for two years. Half of the respondents (50%) described their experience in adult clinics as “good”. Half of the patients were unable to contact their dietitians with questions or concerns, and only 24% considered that they received adequate support. Clinic reviews usually included anthropometric (82%) and dietary assessments (64%), discussion on management of PKU in daily life (78%) and a blood test (71%). Eighty-eight per cent reported they had at least one neurocognitive, mental health or behavioural co-morbidity but less than half of the patients reported an assessment on their neurocognitive functioning or mental health issues. Adult male patients appeared to have less detailed clinic review than females. Less than half (44%) of the respondents reported that they performed a blood spot for blood Phe at least monthly, but only 32% considered they had been informed about the risk of high Phe levels in adulthood. Although time, cost and stress related to travelling were barriers to a face-to-face review, more than 40% of patients had concerns about remote appointments. The frequency and extent of monitoring of adults with PKU, attending specialist adult services, were less than those specified by the PKU European guidelines. The care of women of reproductive age is prioritised over men. Adult metabolic health services require further attention, development and resources to provide a high standard and equitable service to patients with PKU.
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Open AccessArticle
Impact on Diet Quality and Burden of Care in Sapropterin Dihydrochloride Use in Children with Phenylketonuria: A 6 Month Follow-Up Report
by
Maria Inês Gama, Anne Daly, Catherine Ashmore, Sharon Evans, André Moreira-Rosário, Júlio César Rocha and Anita MacDonald
Cited by 2 | Viewed by 1954
Abstract
Introduction: In phenylketonuria (PKU) changes in dietary patterns and behaviors in sapropterin-responsive populations have not been widely reported. We aimed to assess changes in food quality, mental health and burden of care in a paediatric PKU sapropterin-responsive cohort. Methods: In an observational, longitudinal
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Introduction: In phenylketonuria (PKU) changes in dietary patterns and behaviors in sapropterin-responsive populations have not been widely reported. We aimed to assess changes in food quality, mental health and burden of care in a paediatric PKU sapropterin-responsive cohort. Methods: In an observational, longitudinal study, patient questionnaires on food frequency, neophobia, anxiety and depression, impact on family and burden of care were applied at baseline, 3 and 6-months post successful sapropterin-responsiveness testing (defined as a 30% reduction in blood phenylalanine levels). Results: 17 children (10.8 ± 4.2 years) completed 6-months follow-up. Patients body mass index (BMI) z-scores remained unchanged after sapropterin initiation. Blood phenylalanine was stable. Natural protein increased (
p < 0.001) and protein substitute intake decreased (
p = 0.002). There were increases in regular cow’s milk (
p = 0.001), meat/fish, eggs (
p = 0.005), bread (
p = 0.01) and pasta (
p = 0.011) intakes but special low-protein foods intake decreased. Anxiety (
p = 0.016) and depression (
p = 0.022) decreased in caregivers. The impact-on-family, familial-social impact (
p = 0.002) and personal strain (
p = 0.001) lessened. After sapropterin, caregivers spent less time on PKU tasks, the majority ate meals outside the home more regularly and fewer caregivers had to deny food choices to their children. Conclusion: There were significant positive changes in food patterns, behaviors and burden of care in children with PKU and their families after 6-months on sapropterin treatment.
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Open AccessReview
Phenylalanine Tolerance over Time in Phenylketonuria: A Systematic Review and Meta-Analysis
by
Alex Pinto, Fatma Ilgaz, Sharon Evans, Esther van Dam, Júlio César Rocha, Erdem Karabulut, Mary Hickson, Anne Daly and Anita MacDonald
Cited by 4 | Viewed by 3054
Abstract
In phenylketonuria (PKU), natural protein tolerance is defined as the maximum natural protein intake maintaining a blood phenylalanine (Phe) concentration within a target therapeutic range. Tolerance is affected by several factors, and it may differ throughout a person’s lifespan. Data on lifelong Phe/natural
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In phenylketonuria (PKU), natural protein tolerance is defined as the maximum natural protein intake maintaining a blood phenylalanine (Phe) concentration within a target therapeutic range. Tolerance is affected by several factors, and it may differ throughout a person’s lifespan. Data on lifelong Phe/natural protein tolerance are limited and mostly reported in studies with low subject numbers. This systematic review aimed to investigate how Phe/natural protein tolerance changes from birth to adulthood in well-controlled patients with PKU on a Phe-restricted diet. Five electronic databases were searched for articles published until July 2020. From a total of 1334 results, 37 articles met the eligibility criteria (
n = 2464 patients), and 18 were included in the meta-analysis. The mean Phe (mg/day) and natural protein (g/day) intake gradually increased from birth until 6 y (at the age of 6 months, the mean Phe intake was 267 mg/day, and natural protein intake was 5.4 g/day; at the age of 5 y, the mean Phe intake was 377 mg/day, and the natural protein intake was 8.9 g/day). However, an increase in Phe/natural protein tolerance was more apparent at the beginning of late childhood and was >1.5-fold that of the Phe tolerance in early childhood. During the pubertal growth spurt, the mean natural protein/Phe tolerance was approximately three times higher than in the first year of life, reaching a mean Phe intake of 709 mg/day and a mean natural protein intake of 18 g/day. Post adolescence, a pooled analysis could only be performed for natural protein intake. The mean natural protein tolerance reached its highest (32.4 g/day) point at the age of 17 y and remained consistent (31.6 g/day) in adulthood, but limited data were available. The results of the meta-analysis showed that Phe/natural protein tolerance (expressed as mg or g per day) increases with age, particularly at the beginning of puberty, and reaches its highest level at the end of adolescence. This needs to be interpreted with caution as limited data were available in adult patients. There was also a high degree of heterogeneity between studies due to differences in sample size, the severity of PKU, and target therapeutic levels for blood Phe control.
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Open AccessArticle
Preliminary Data on Free Use of Fruits and Vegetables Containing Phenylalanine 76–100 mg/100 g of Food in 16 Children with Phenylketonuria: 6 Months Follow-Up
by
Alex Pinto, Anne Daly, Júlio César Rocha, Catherine Ashmore, Sharon Evans, Richard Jackson, Mary Hickson and Anita MacDonald
Cited by 1 | Viewed by 2012
Abstract
In phenylketonuria (PKU), a previous intervention study assessing the patients ability to tolerate fruits and vegetables containing phenylalanine 76–100 mg/100 g without limit or measurement, found that an extra 50 mg/day phenylalanine, but not 100 mg/day, was tolerated from these fruits and vegetables.
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In phenylketonuria (PKU), a previous intervention study assessing the patients ability to tolerate fruits and vegetables containing phenylalanine 76–100 mg/100 g without limit or measurement, found that an extra 50 mg/day phenylalanine, but not 100 mg/day, was tolerated from these fruits and vegetables. In a further 6-month extension study, we examined the effect of the ‘free’ use of this group of fruits and vegetables on blood phenylalanine control. For 6 months, the patients ate fruits and vegetables containing phenylalanine 76–100 mg/100 g without limit or measurement. Three-day diet diaries and the patients’ weights were collected monthly. Blood phenylalanine spots were collected weekly aiming for blood phenylalanine levels <360 μmol/L. Retrospective blood phenylalanine was collected 6 months pre-trial. All 16 patients (69% females) from the intervention study took part in the extension study. Most of the patients (
n = 14/16) had classical PKU with a median age of 10.5 years (range: 6–13). There was no statistically significant difference in the median blood phenylalanine pre-study (270, range: 50–760 μmol/L) compared to the 6-month extension study (250, range: 20–750 μmol/L) (
p= 0.4867). The patients had a median of 21 and 22 bloodspots, pre- and post-trial, respectively. In the extension study, the patients had an actual mean intake of 11 g/day (4–37) natural protein and 65 g/day (60–80) protein equivalent from a protein substitute. The mean phenylalanine intake was 563 mg/day (200–1850) with only 19 mg/day (0–146) phenylalanine from fruits and vegetables containing phenylalanine 76–100 mg/100 g. The weight z-scores remained unchanged (1.52 vs. 1.60,
p = 0.4715). There was no adverse impact on blood phenylalanine control when fruits and vegetables containing phenylalanine 76–100 mg/100 g were eaten without limit or measurement. However, the fruits and vegetable portion sizes eaten were small (60 g/week). Further longitudinal work is necessary to examine the ‘free’ use of fruits and vegetables containing phenylalanine 76–100 mg/100 g on metabolic control in patients with PKU.
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