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Background: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine.Main Body: In 2017 the first European PKU Guidelines were published. These guidelines contained evidence based and/or expert opinion recommendations regarding diagnosis, treatment and care for patients with PKU of all ages. This manuscript is a supplement containing the practical application of the dietary treatment.Conclusion: This handbook can support dietitians, nutritionists and physicians in starting, adjusting and maintaining dietary treatment. [ABSTRACT FROM AUTHOR]

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. If left untreated, PKU results in increased phenylalanine concentrations in blood and brain, which cause severe intellectual disability, epilepsy and behavioural problems. PKU management differs widely across Europe and therefore these guidelines have been developed aiming to optimize and standardize PKU care. Professionals from 10 different European countries developed the guidelines according to the AGREE (Appraisal of Guidelines for Research and Evaluation) method. Literature search, critical appraisal and evidence grading were conducted according to the SIGN (Scottish Intercollegiate Guidelines Network) method. The Delphi-method was used when there was no or little evidence available. External consultants reviewed the guidelines. Using these methods 70 statements were formulated based on the highest quality evidence available. The level of evidence of most recommendations is C or D. Although study designs and patient numbers are sub-optimal, many statements are convincing, important and relevant. In addition, knowledge gaps are identified which require further research in order to direct better care for the future. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Abstract: In recent years our understanding of the follow up policies for PKU has increased substantially. In particular, we now understand the importance of maintaining control of blood phenylalanine (phe) concentrations life-long to achieve the best long-term neuropsychological outcomes. The concordance with the follow up strategy remains a key challenge for the future, especially with respect to adolescents and young adults. The recent therapies could ease the burden of the dietary phe restriction for PKU patients and their families. The time may be right for revisiting the guidelines for follow up of PKU in order to address a number of important issues related to PKU management: promotion of breastfeeding to complementary feeding up to 2years of age for prevention of early growth retardation and later overweight development, treatment advancements for metabolic control, blood phe and tyr variability, routine screening measures for nutritional biomarkers, neurocognitive and psychological assessments, bone pathology, understanding the challenges of compliance and transitioning into adulthood as an individual with PKU and addressing unmet needs in this population. [Copyright &y& Elsevier]

A subset of patients with phenylketonuria benefit from treatment with tetrahydrobiopterin (BH 4), although there is no consensus on the definition of BH 4 responsiveness. The aim of this study therefore was to gain insight into the definitions of long-term BH 4 responsiveness being used around the world. We performed a web-based survey targeting healthcare professionals involved in the treatment of PKU patients. Data were analysed according to geographical region (Europe, USA/Canada, other). We analysed 166 responses. Long-term BH 4 responsiveness was commonly defined using natural protein tolerance (95.6%), improvement of metabolic control (73.5%) and increase in quality of life (48.2%). When a specific value for a reduction in phenylalanine concentrations was reported (n = 89), 30% and 20% were most frequently used as cut-off values (76% and 19% of respondents, respectively). When a specific relative increase in natural protein tolerance was used to define long-term BH 4 responsiveness (n = 71), respondents most commonly reported cut-off values of 30% and 100% (28% of respondents in both cases). Respondents from USA/Canada (n = 50) generally used less strict cut-off values compared to Europe (n = 96). Furthermore, respondents working within the same center answered differently. The results of this study suggest a very heterogeneous situation on the topic of defining long-term BH 4 responsiveness, not only at a worldwide level but also within centers. Developing a strong evidence- and consensus-based definition would improve the quality of BH 4 treatment. [ABSTRACT FROM AUTHOR]

Introduction The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, retrospective cohort study. Methods Diagnostic age of PKU and co-existent condition, treatment regimen, and impact of co-existent condition on blood phenylalanine (Phe) control and PKU management were reported. Results 30 patients (11 males and 19 females), with PKU and a co-existent condition, current median age of 14 years (range 0.4 to 40 years) from 13 treatment centres from Europe and Turkey were described. There were 21 co-existent conditions with PKU; 9 were autoimmune; 6 gastrointestinal, 3 chromosomal abnormalities, and 3 inherited conditions. There were only 5 cases of parental consanguinity. Some patients required conflicting diet therapy (n = 5), nutritional support (n = 7) and 5 children had feeding problems. There was delayed diagnosis of co-existent conditions (n = 3); delayed treatment of PKU (n = 1) and amenorrhea associated with Grave's disease that masked a PKU pregnancy for 12 weeks. Co-existent conditions adversely affected blood Phe control in 47% (n = 14) of patients. Some co-existent conditions increased the complexity of disease management and increased management burden for patients and caregivers. Conclusions Occurrence of co-existent disease is not uncommon in patients with PKU and so investigation for co-existent disorders when the clinical history is not completely consistent with PKU is essential. Integrating care of a second condition with PKU management is challenging. [ABSTRACT FROM AUTHOR]