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Background: In phenylketonuria (PKU), attending multidisciplinary clinic reviews is an important aspect of life-long care. Since the COVID-19 pandemic, video and telephone clinics are used as alternative methods for people with PKU to have contact with their care team. There is limited research concerning patient preference, experience and perceptions of alternative types of clinic review. Individuals from the UK with PKU and their caregivers were invited to complete an online questionnaire, hosted on the National Society for PKU (NSPKU) website and social media platform., Results: Data was available from 203 respondents. Forty one per cent of respondents (n = 49/119) preferred in-person clinics; 41% (n = 49) a hybrid of in-person, video and telephone clinics; 9% (n = 11) video clinics only, 6% (n = 7) telephone only and 3% (n = 3) were unsure. The main respondent obstacles to in-person clinics were costs, travel and time, but this was balanced by the benefits of a physical examination and better patient engagement/motivation. Twenty one per cent (n = 36/169) of respondents were uncomfortable with the number of healthcare professionals (HCPs) in a clinic room. Patients were less likely to consult with a doctor on video (64%, n = 91/143) or phone (50%, n = 59/119) reviews compared to in-person (80%, n = 146/183). Issues with video and telephone reviews included the shorter time length of review, distractions, technical issues and poor patient engagement., Conclusions: Online video and telephone clinic platforms were effective in overcoming the challenging circumstances in management, monitoring and treatment of patients with PKU during the COVID-19 pandemic. However, in-person clinics remain the preferred respondent option. It is important that HCPs are flexible, enabling people with PKU a choice of clinic options according to their individual clinical need and circumstances., (© 2024. The Author(s).)

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.

Phenylketonuria remains one of the most common inborn errors in the United Kingdom. It is detected on the newborn heel-prick screening sample allowing early treatment with a strict low phenylalanine diet supplemented with artificial amino acids, and appropriate vitamin and minerals. Although the long-term prognosis is good, there is an increasing body of evidence highlighting subtle problems in neuropsychological function with slower reaction times and poorer executive function than peers. White matter changes clearly seen on brain magnetic resonance imaging may have some relationship to these neuropsychological difficulties but their significance is not clearly understood. The diet, although successful, is difficult to follow lifelong and with its attendant risks of nutritional deficiencies needs careful specialist management. In view of these challenges new treatments such as sapropterin (a tetrahydrobiopterin analogue) and large neutral amino acids are currently being used in phenylketonuria and a human trial has started using ammonia lyase as enzyme replacement therapy. Maternal phenylketonuria syndrome remains a risk for those who conceive whilst blood phenylalanine is elevated and females must be counselled early in childhood to avoid this risk. [ABSTRACT FROM AUTHOR]

Background To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. Results Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received. Conclusion The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet. [ABSTRACT FROM AUTHOR]

Abstract: Phenylketonuria remains one of the most common inborn errors in the United Kingdom. It is detected on the newborn heel-prick screening sample allowing early treatment with a strict low phenylalanine diet supplemented with artificial amino acids, and appropriate vitamin and minerals. Although the long-term prognosis is good, there is an increasing body of evidence highlighting subtle problems in neuropsychological function with slower reaction times and poorer executive function than peers. White matter changes clearly seen on brain magnetic resonance imaging may have some relationship to these neuropsychological difficulties but their significance is not clearly understood. The diet, although successful, is difficult to follow lifelong and with its attendant risks of nutritional deficiencies needs careful specialist management. In view of these challenges new treatments such as sapropterin (a tetrahydrobiopterin analogue) and large neutral amino acids are currently being used in phenylketonuria and a human trial has started using ammonia lyase as enzyme replacement therapy. Maternal phenylketonuria syndrome remains a risk for those who conceive whilst blood phe is elevated and females must be counselled early in childhood to avoid this risk. [Copyright &y& Elsevier]

Previous studies have suggested that cognitive and psychosocial underfunctioning in early-treated adults with phenylketonuria (PKU) may be explained by suboptimal adherence to dietary treatments, however, these studies often employ small samples, with different outcome measures, definitions and cut-offs. Samples have also tended to comprise participants with a limited range of blood phenylalanine concentrations, and often individuals who may not have been treated early enough to avoid neurological damage. In this study, we explore the impact of lifetime dietary control, as indicated by blood phenylalanine concentrations in childhood, adolescence and adulthood, on long-term cognitive and psychosocial outcomes in a large sample of adults with PKU who were diagnosed by neonatal screening and commenced on dietary treatment within the first month of life. One hundred and fifty-four participants underwent cognitive testing, assessing attention, learning, working memory, language, executive functioning and processing speed. One hundred and forty-nine completed measures of psychosocial functioning, documenting educational, occupational, quality of life, emotional and social outcomes which were compared with a group of healthy controls. Many adults with PKU demonstrated cognitive impairments, most frequently affecting processing speed (23%), executive function (20%) and learning (12%). Cognitive outcomes were related to measures of historic metabolic control, but only processing speed was significantly related to phenylalanine concentration at the time of testing after controlling for historic levels. Adults with PKU did not, however, differ from controls in educational, occupational, quality of life or emotional outcomes, or on a measure of family functioning, and showed only minor differences in relationship style. These findings have implications for patient counselling and decisions regarding the management of PKU in adulthood., (© 2021 SSIEM.)

Children spend a substantial part of their childhood in school, so provision of dietary care and inclusion of children with phenylketonuria (PKU) in this setting is essential. There are no reports describing the dietary support children with PKU receive whilst at school. The aim of this cross-sectional study was to explore the experiences of the dietary management of children with PKU in schools across the UK. Data was collected using an online survey completed by parents/caregivers of children with PKU. Of 159 questionnaire responses, 92% ( n = 146) of children attended state school, 6% ( n = 10) private school and 2% ( n = 3) other. Fourteen per cent ( n = 21/154) were at nursery/preschool, 51% ( n = 79/154) primary and 35% ( n = 54/154) secondary school. Sixty-one per cent ( n = 97/159) said their child did not have school meals, with some catering services refusing to provide suitable food and some parents distrusting the school meals service. Sixty-one per cent of children had an individual health care plan (IHCP) ( n = 95/155). Children were commonly unsupervised at lunchtime (40%, n = 63/159), with snacks (46%, n = 71/155) and protein substitute (30%, n = 47/157), with significantly less supervision in secondary than primary school ( p < 0.001). An IHCP was significantly associated with improved supervision of food and protein substitute administration ( p < 0.01), and better communication between parents/caregivers and the school team ( p < 0.05). Children commonly accessed non-permitted foods in school. Therefore, parents/caregivers described important issues concerning the school provision of low phenylalanine food and protein substitute. Every child should have an IHCP which details their dietary needs and how these will be met safely and discreetly. It is imperative that children with PKU are supported in school.

We aimed to assess if the same cognitive batteries can be used cross-nationally to monitor the effect of Phenylketonuria (PKU). We assessed whether a battery, previously used with English adults with PKU (AwPKU), was also sensitive to impairments in Italian AwPKU. From our original battery, we selected a number of tasks that comprehensively assessed visual attention, visuo-motor coordination, executive functions (particularly, reasoning, planning, and monitoring), sustained attention, and verbal and visual memory and learning. When verbal stimuli/or responses were involved, stimuli were closely matched between the two languages for psycholinguistic variables. We administered the tasks to 19 Italian AwPKU and 19 Italian matched controls and compared results from with 19 English AwPKU and 19 English matched controls selected from a previously tested cohort. Participant election was blind to cognitive performance and metabolic control, but participants were closely matched for age and education. The Italian AwPKU group had slightly worse metabolic control but showed levels of performance and patterns of impairment similar to the English AwPKU group. The Italian results also showed extensive correlations between adult cognitive measures and metabolic measures across the life span, both in terms of Phenylalanine (Phe) levels and Phe fluctuations, replicating previous results in English. These results suggest that batteries with the same and/or matched tasks can be used to assess cognitive outcomes across countries allowing results to be compared and accrued. Future studies should explore potential differences in metabolic control across countries to understand what variables make metabolic control easier to achieve.

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 D 3 , 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 B 6 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.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., Competing Interests: BG, RB, HC, GH and RS are employees of Nutricia Ltd. Have received educational grants from Nutricia Ltd for conference attendance: SA (Sarah Adam), CN, SA (Sandra Adams), CD, MH, KKH, RS (Rachel Skeath), PH, LG, CF and CN. Have received honorarium from Nutricia Ltd for conference presentation: SA (Sandra Adams), LR and LG. Have provided scientific advice and expertise for Nutricia Advisory Boards: YR, SA (Sarah Adam), LR, CD, KKH, CF and CN. Declare no competing interests with the study funder: SF, FJ, CD, AC, IH, SD, AS, VB.