Introducing a granule based protein substitute to the diet of a child with phenylketonuria to address reluctance to ingest phenylalanine-free protein substitute: A case report.

Phenylalanine (Phe)-free protein substitutes are used within the management of phenylketonuria (PKU). However, adherence to the Phe-restricted diet is often challenging. A child (age 4.5 years) with PKU rejected the Phe-free protein substitutes used within her therapeutic diet, causing stress for herself and family at mealtimes. Switching to a new Phe-free protein substitute that can be mixed into other foods [PKU GOLIKE® (3-16)] provided an alternative strategy that was acceptable to the child. Good control of blood Phe was maintained. Newer Phe-free protein substitutes may provide a strategy for maintaining the therapeutic diet for PKU where the patient has difficulty doing so on standard substitutes. Here, the use of a Phe-free protein substitute with improved palatability and ease of use supported maintenance of the Phe-restricted diet for a child with PKU who struggled to maintain the diet on standard substitutes.

Evaluation of a New Glycomacropeptide-Based Protein Substitute in Powdered and Liquid Format in Patients with PKU.

(1) Background: Good adherence to a Phe-restricted diet supplemented with an adequate amount of a protein substitute (PS) is important for good clinical outcomes in PKU. Glycomacropeptide (cGMP)-PSs are innovative, palatable alternatives to amino acid-based PSs (AA-PS). This study aimed to evaluate a new cGMP-PS in liquid and powder formats in PKU. (2) Methods: Children and adults with PKU recruited from eight centres were prescribed at least one serving/day of cGMP-PS for 7-28 days. Adherence, acceptability, and gastrointestinal tolerance were recorded at baseline and the end of the intervention. The blood Phe levels reported as part of routine care during the intervention were recorded. (3) Results: In total, 23 patients (powder group, n = 13; liquid group, n = 10) completed the study. The majority assessed the products to be palatable (77% of powder group; 100% of liquid group) and well tolerated; the adherence to the product prescription was good. A total of 14 patients provided blood Phe results during the intervention, which were within the target therapeutic range for most patients (n = 11) at baseline and during the intervention. (4) Conclusions: These new cGMP-PSs were well accepted and tolerated, and their use did not adversely affect blood Phe control.

Evaluation of a New 'Mix-In' Style Glycomacropeptide-Based Protein Substitute for Food and Drinks in Patients with Phenylketonuria and Tyrosinemia.

(1) Background: Poor palatability, large volume, and lack of variety of some liquid and powdered protein substitutes (PSs) for patients with phenylketonuria (PKU) and tyrosinemia (TYR) can result in poor adherence. This study aimed to evaluate a new unflavoured, powdered GMP-based PS designed to be mixed into drinks, foods, or with other PSs, in patients with PKU and TYR. (2) Methods: Paediatric and adult community-based patients were recruited from eight metabolic centres and prescribed ≥1 sachet/day (10 g protein equivalent (PE)) of the Mix-In-style PS over 28 days. Adherence, palatability, GI tolerance, and metabolic control were recorded at baseline and follow-up. Patients who completed at least 7 days of intervention were included in the final analysis. (3) Results: Eighteen patients (3-45 years, nine males) with PKU (n = 12) and TYR (n = 6) used the Mix-In-style PS for ≥7 days (mean 26.4 days (SD 4.6), range 11-28 days) alongside their previous PS, with a mean intake of 16.7 g (SD 7.7) PE/day. Adherence was 86% (SD 25), and GI tolerance was stable, with n = 14 experiencing no/no new symptoms and n = 3 showing improved symptoms compared to baseline. Overall palatability was rated satisfactory by 78% of patients, who successfully used the Mix-In-style PS in various foods and drinks, including smoothies, squash, and milk alternatives, as a top-up to meet their protein needs. There was no concern regarding safety/metabolic control during the intervention. (4) Conclusions: The 'Mix-In'-style PS was well adhered to, accepted, and tolerated. Collectively, these data show that providing a flexible, convenient, and novel format of PS can help with adherence and meet patients' protein needs.

Suitability and Allocation of Protein-Containing Foods According to Protein Tolerance in PKU: A 2022 UK National Consensus.

Introduction: There is little practical guidance about suitable food choices for higher natural protein tolerances in patients with phenylketonuria (PKU). This is particularly important to consider with the introduction of adjunct pharmaceutical treatments that may improve protein tolerance. Aim: To develop a set of guidelines for the introduction of higher protein foods into the diets of patients with PKU who tolerate >10 g/day of protein. Methods: In January 2022, a 26-item food group questionnaire, listing a range of foods containing protein from 5 to >20 g/100 g, was sent to all British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 80; 26 Inherited Metabolic Disease [IMD] centres). They were asked to consider within their IMD dietetic team when they would recommend introducing each of the 26 protein-containing food groups into a patient's diet who tolerated >10 g to 60 g/day of protein. The patient protein tolerance for each food group that received the majority vote from IMD dietetic teams was chosen as its tolerance threshold for introduction. A virtual meeting was held using Delphi methodology in March 2022 to discuss and agree final consensus. Results: Responses were received from dietitians from 22/26 IMD centres (85%) (11 paediatric, 11 adult). For patients tolerating protein ≥15 g/day, the following foods were agreed for inclusion: gluten-free pastas, gluten-free flours, regular bread, cheese spreads, soft cheese, and lentils in brine; for protein tolerance ≥20 g/day: nuts, hard cheeses, regular flours, meat/fish, and plant-based alternative products (containing 5−10 g/100 g protein), regular pasta, seeds, eggs, dried legumes, and yeast extract spreads were added; for protein tolerance ≥30 g/day: meat/fish and plant-based alternative products (containing >10−20 g/100 g protein) were added; and for protein tolerance ≥40 g/day: meat/fish and plant-based alternatives (containing >20 g/100 g protein) were added. Conclusion: This UK consensus by IMD dietitians from 22 UK centres describes for the first time the suitability and allocation of higher protein foods according to individual patient protein tolerance. It provides valuable guidance for health professionals to enable them to standardize practice and give rational advice to patients.

Special Low Protein Foods Prescribed in England for PKU Patients: An Analysis of Prescribing Patterns and Cost.

Patients with phenylketonuria (PKU) are reliant on special low protein foods (SLPFs) as part of their dietary treatment. In England, several issues regarding the accessibility of SLPFs through the national prescribing system have been highlighted. Therefore, prescribing patterns and expenditure on all SLPFs available on prescription in England (n = 142) were examined. Their costs in comparison to regular protein-containing (n = 182) and 'free-from' products (n = 135) were also analysed. Similar foods were grouped into subgroups (n = 40). The number of units and costs of SLPFs prescribed in total and per subgroup from January to December 2020 were calculated using National Health Service (NHS) Business Service Authority (NHSBSA) ePACT2 (electronic Prescribing Analysis and Cost Tool) for England. Monthly patient SLPF units prescribed were calculated using patient numbers with PKU and non-PKU inherited metabolic disorders (IMD) consuming SLPFs. This was compared to the National Society for PKU (NSPKU) prescribing guidance. Ninety-eight percent of SLPF subgroups (n = 39/40) were more expensive than regular and 'free-from' food subgroups. However, costs to prescribe SLPFs are significantly less than theoretical calculations. From January to December 2020, 208,932 units of SLPFs were prescribed (excluding milk replacers), costing the NHS £2,151,973 (including milk replacers). This equates to £962 per patient annually, and prescribed amounts are well below the upper limits suggested by the NSPKU, indicating under prescribing of SLPFs. It is recommended that a simpler and improved system should be implemented. Ideally, specialist metabolic dietitians should have responsibility for prescribing SLPFs. This would ensure that patients with PKU have the necessary access to their essential dietary treatment, which, in turn, should help promote dietary adherence and improve metabolic control.

Dietary Management, Clinical Status and Outcome of Patients with Citrin Deficiency in the UK.

BACKGROUND: Little is known about the optimal dietary treatment for citrin deficiency. Our aim is to describe the management of UK citrin deficiency patients. METHODS: A longitudinal retrospective review was performed. Data were collected from medical records on presenting signs and symptoms, dietary management and clinical outcome. RESULTS: data were collected on 32 patients from 21 families. 50% were females (16/32). Median age at diagnosis was 4 y (5 days-35 y) with 12 patients diagnosed in the neonatal period with neonatal intrahepatic cholestasis (NICCD), eight later in childhood (FTTDCD) and 12 by family screening based on index cases from five families. No patient had adult-onset type II citrullinemia. The patient age at the time of data collection was a median of 11 y (1-44 y). 91% (29/32) of patients had normal physical and neurological development, 47% (15/32) experienced recurrent unexplained abdominal pain and 9% (3/32) episodes of hypoglycaemia. Siblings had different phenotypes (5 families had > 1 affected patient). Most patients preferred high protein foods, limiting sugar-containing foods. Only 41% (13/32) were prescribed a low CHO, high protein, high fat diet (restriction varied) and two used medium chain triglyceride (MCT) supplements. No patient was prescribed drug therapy. Twenty-five per cent (8/32) of patients were underweight and 41% (13/32) had height <-1 z-scores. CONCLUSIONS: patients presented with various phenotypes, symptoms and suboptimal growth. Symptoms and biochemical markers improved with age, but height remained low in some. More research is necessary to assess the effectiveness of dietary approaches in improving clinical outcomes and symptoms in citrin deficiency.

Uniformity of Food Protein Interpretation Amongst Dietitians for Patients with Phenylketonuria (PKU): 2020 UK National Consensus Statements.

In phenylketonuria (PKU), variable dietary advice provided by health professionals and social media leads to uncertainty for patients/caregivers reliant on accurate, evidence based dietary information. Over four years, 112 consensus statements concerning the allocation of foods in a low phenylalanine diet for PKU were developed by the British Inherited Metabolic Disease Dietitians Group (BIMDG-DG) from 34 PKU treatment centres, utilising 10 rounds of Delphi consultation to gain a majority (≥75%) decision. A mean of 29 UK dietitians (range: 18-40) and 18 treatment centres (range: 13-23) contributed in each round. Statements encompassed all foods/food groups divided into four categories based on defined protein/phenylalanine content: (1) foods high in protein/phenylalanine (best avoided); (2) foods allowed without restriction including fruit/vegetables containing phenylalanine ≤75 mg/100 g and most foods containing protein ≤0.5 g/100 g; (3) foods that should be calculated/weighed as an exchange food if they contain protein exchange ingredients (categorized into foods with a protein content of: >0.1 g/100 g (milk/plant milks only), >0.5 g/100 g (bread/pasta/cereal/flours), >1 g/100 g (cook-in/table-top sauces/dressings), >1.5 g/100 g (soya sauces)); and (4) fruit/vegetables containing phenylalanine >75 mg/100 g allocated as part of the protein/phenylalanine exchange system. These statements have been endorsed and translated into practical dietary management advice by the medical advisory dietitians for the National Society for PKU (NSPKU).

Nutritional and Metabolic Characteristics of UK Adult Phenylketonuria Patients with Varying Dietary Adherence.

The nutritional and metabolic characteristics of adult phenylketonuria (PKU) patients in the UK with varying dietary adherence is unknown. In other countries, nutritional and metabolic abnormalities have been reported in nonadherent patients compared to adherent counterparts. A pooled analysis of primary baseline data from two UK multi-centre studies was therefore performed to establish whether this is true from a UK perspective. Adult PKU patients who had provided 3-day food records and amino acid blood samples were included and grouped according to dietary adherence (adherent; n = 16 vs. nonadherent; n = 14). Nonadherent patients consumed greater amounts of natural protein compared to adherent patients (61.6 ± 30.7 vs. 18.3 ± 7.7 g/day; q < 0.001). In contrast, the contribution of protein substitutes to total protein intake was lower in nonadherent compared to adherent patients (3.9 ± 9.2 g/day vs. 58.6 ± 10.2 g/day; q < 0.001). Intakes of iron, zinc, vitamin D3, magnesium, calcium, selenium, iodine, vitamin C, vitamin A and copper were significantly lower in nonadherent compared to adherent patients and were below UK Reference Nutrient Intakes. Similarly, intakes of thiamin, riboflavin, niacin, vitamin B6 and phosphorus were significantly lower in nonadherent compared to adherent patients but met the UK Reference Nutrient Intakes. Phenylalanine concentrations in nonadherent patients were significantly higher than adherent patients (861 ± 348 vs. 464 ± 196 µmol/L; q=0.040) and fell outside of European treatment target ranges. This study shows the nutritional and metabolic consequences of deviation from phenylalanine restriction and intake of PKU protein substitutes in nonadherent adult PKU patients. Collectively, these data further underlie the importance of life-long adherence to the PKU diet.

Development of national consensus statements on food labelling interpretation and protein allocation in a low phenylalanine diet for PKU.

BACKGROUND: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients. METHODOLOGY: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added. RESULTS: The statements incorporated controversial dietary topics including: a practical 'scale' for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians (n = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% (n = 26/36) and 64% (n = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU. CONCLUSIONS: The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.