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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.

ContextFamilial partial lipodystrophy type 1 (FPLD1) is an extreme form of central adiposity, with peripheral lipodystrophy associated with severe manifestations of the metabolic syndrome, often poorly responsive to standard therapeutic approaches. Body mass index in FPLD1 varies but, in many cases, is below the level at which metabolic surgery is usually considered as a therapeutic option.DesignWe detailed the metabolic response to gastric bypass surgery of three patients with FPLD1, refractory to medical therapy.ResultsRoux-en-Y gastric bypass (RYGB) was associated with weight loss and substantial improvements in glycemic control and insulin sensitivity. All three patients were able to stop using insulin. Glucose tolerance testing in one patient demonstrated an increase in L-cell–derived gut hormone responses postoperatively.ConclusionRYGB surgery substantially improved glycemic control in three patients with FPLD1, two of whom had body mass indices below 30 kg/m2. RYGB should be considered in patients with partial lipodystrophy and refractory metabolic disease.We studied the clinical response of three patients with familial partial lipodystrophy type 1 and refractory diabetes to RYGB surgery and documented dramatic clinical improvements.

Background: Special low-protein foods are essential in the dietary treatment of phenylketonuria (PKU). In the UK, these are available on prescription through the General Practitioners (GPs) and distributed via nutritional home delivery companies or pharmacies. Methods: A 58-item online non-validated semi-structured questionnaire was emailed to British Inherited Metabolic Disease Group (BIMDG) dietitians and dietetic support workers (DSW)/administrators working in PKU to ascertain the main system issues and errors with the supply of low-protein prescription foods (LPPF). Results: 73% (n = 53/73) of dietitians and 72% (n = 18/25) of DSW/administrators responded. A total of 80 questionnaires (representing 44 paediatric and 36 adult PKU centres) were completed. A total of 50% (n = 40/80) of respondents reported patient/caregiver problems accessing LPPF at least weekly. The most common problems were unavailable products (82%), missing LPPF in deliveries (79%), and delayed deliveries (66%). For 64% of respondents, >25% of their patients had recurring problems accessing LPPF, and 69% of respondents spent ≥1 h/week and 11% >5 h/week correcting LPPF patient supply issues. The most common foods patients experienced supply issues with were bread (96%), pasta/rice (41%) and milk replacements (35%). This was associated with GP prescription errors (65%), LPPF prescriptions sent to incorrect dispensers/suppliers (60%), and manufacturer supply issues (54%). Problems with patients/caregivers included not ordering LPPF in a timely way (81%), not responding to messages from home delivery companies (73%) and poor understanding of the ordering process (70%). The majority (93%) of respondents reported that prescription issues impacted their patients’ blood Phe control. Suggestions for improving access to LPPF included centralisation of the system to one supplier (76%) and apps for ordering LPPF (69%). Conclusions: The supply of LPPF for PKU in the UK is problematic; it may adversely affect the ability of patients to adhere to dietary management, and a review investigating patient access to LPPF is urgently required.

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.

(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.

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.

(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.

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.

Funding Information: No funding was required for this project. All work was conducted as part of routine service by all dietitians involved. Publisher Copyright: © 2022 by the authors. 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.

Funding Information: Conflicts of Interest: A.M. (Anita MacDonald) is a member of, the advisory board ELEMENT Danone-Nutricia, the advisory board for Arla and Applied Pharma Research, and received research funding and honoraria from Nutricia, Vitaflo International, Biomarin, MetaHealth, Metax and Merck Serono. S.E. receives research funding from Nutricia, and has received financial support and honoraria from Nutricia and Vitaflo to attend/speak at study days and conferences. A.P. received an educational grant from Cambrooke Therapeutics and grants from Vitaflo International, Nutricia, Merck Serono, Biomarin and Mevalia to attend scientific meetings. A.D. received research funding from Vitaflo International, financial support from Nutricia, Mevalia and Vitaflo International to attend study days and conferences. J.C.R. is a member of the European Nutritionist Expert Panel (Biomarin), the Advisory Board for Applied Pharma Research and Nutricia, and has received honoraria as a speaker from APR, Merck Serono, Biomarin, Nutricia, Vitaflo, Cambrooke, PIAM, and Lifediet. S.F. (Suzanne Ford) is a member of the advisory board for Nutricia, and MetaHealth and has received financial support and honoraria from Cambrooke and Vitaflo. R.S. has received sponsorship to attend conferences and study days, payment to present at conferences from Nutricia Metabolics, Vitaflo Internation and Mevalia. C.E. has received honoraria and educational grants to attend events from Vitaflo, Nutricia, Meta Healthcare and SOBI and is a member of the Advisory Commitee on Borderline Substances. S.F. (Sarah Firman) has received funding to attend conferences and study days from Nutricia, Vitaflo International and Dr. Schär UK Ltd., and consulting fees from Vitaflo International and Meta Healthcare Ltd. C.N. has received financial support and honoraria from Nutricia and Vitaflo to attend/speak at study days and conferences. L.R. is a member of the Nutricia adult advisory board and received honorarium from Nutricia and Vitaflo in the past. F.J.W. receives honoraria, educational and travel grants from Nutricia and Vitaflo. M.H. is a member of advisory board Nutricia Danone and Applied Pharma and has received financial support and honoraria from Nutricia, Vitaflo, Cambrooke, Mevalia, Promin for attendance at conferences/meetings and speakers fee. A.T. (Allyson Terry) has received payment from Vitaflo International for speaking at a patient event. K.vW. receives honoraria and educational grants from Nutricia, Vitaflo and Meta Healthcare. S.T. is expected to receive honoraria from Vitaflo International for providing feedback and reviewing guidelines for PKU Sphere. G.W., M.F., L.G., C.P., S.A., A.M. (Anita MacDonald), A.T. (Alison Tooke), A.W., E.G., L.W., I.H., H.S., J.G., A.E., S.C., R.P. have no conflicts of interest to declare. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. 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.