Recommendations for the nutrition management of phenylalanine hydroxylase deficiency (original) (raw)
Related papers
Current Paediatrics, 2004
Phenylketonuria (PKU), one of the commonest inherited metabolic disorders, is caused by deficiency of the enzyme phenylalanine hydroxylase (PAH). To date, over 460 different mutations in the PAH gene have been described. PAH deficiency results in failure of hydroxylation of phenylalanine to tyrosine. Raised body levels of phenylalanine interfere with normal brain development in infancy and childhood. For over 30 years, there has been a newborn screening programme for PKU. Early detection combined with an effective dietary treatment results in normal development for affected individuals. Although relaxation of diet after childhood has little or no detrimental effect upon intelligence, the current recommendation in the UK is for such treatment to be continued into adulthood. Women with PKU must be under strict dietary control at the time of conception and during pregnancy in order to prevent damage to the fetus. Although new therapies are being investigated, they are unlikely to replace the need for dietary treatment in the foreseeable future.
Changing dietary practices in phenylketonuria
The Turkish journal of pediatrics
In recent years, there has been much focus on research on non-dietary treatments in phenylketonuria (PKU). However, diet is likely to remain the major treatment for many years to come, since it has continued to be developed and consistent improvements have occurred. For example, with protein substitute, studies have tried to define the optimal dose and timing of intake; changes in palatability and presentation appear to have led to the long-term maintenance of acceptable blood phenylalanine control in teenage patients, and the low phenylalanine protein source glycomacropeptide is being considered as an alternative source to non-phenylalanine amino acids. Some countries are now adopting a simpler approach to dietary management, allowing a wider range of lower low phenylalanine foods without measurement, in combination with controlled phenylalanine exchange systems. Patients with PKU who are partially responsive to sapropterin dihydrochloride still require some dietary treatment. Long...
Phenylketonuria: questioning the gospel
Expert Review of Endocrinology & Metabolism, 2007
Phenylketonuria (PKU) was first described over 70 years ago, treatment was developed 50 years ago and universal newborn PKU screening was introduced 40 years ago. Phenylalanine-restricted dietary treatment has prevented mental retardation in thousands of individuals worldwide. We acknowledge, however, that there is still much to learn in the field. The incidence of mental retardation in untreated PKU is likely to be considerably less than the original estimates. Since dietary control is suboptimal in late childhood, adolescence and adulthood, alternative methods of treatment are being explored. These include large neutral amino acids, phenylalanine ammonia lyase, tetrahydrobiopterin and gene replacement. Evidence has surfaced that the semisynthetic, low-protein diet used to treat PKU may be deficient in certain important nutrients. Maternal PKU treatment may be successful even if initiated as late as 8-10 weeks into pregnancy. A plea is made for the immediate establishment of adult treatment centers for PKU (and other inherited metabolic diseases) for long-term treatment, follow-up and research.
Molecular Genetics and Metabolism, 2007
Blood phenylalanine (Phe) levels provide a practical and reliable method for the diagnosis and monitoring of metabolic status in patients with phenylketonuria (PKU). To assess the reliability of blood Phe levels as a predictive biomarker of clinical outcomes in the development of treatments for PKU, a systematic literature review and meta-analysis of published trials of PKU, which included Phe level and neurological and dietary compliance outcome measures, was conducted. Within-study correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies. Significant, proportional correlations were found during critical periods (from 0 to 12 years of age) for early-treated patients with PKU (r = À0.35; 95% confidence interval [CI]: À0.44 to À0.27), where each 100 lmol/l increase in Phe predicted a 1.3-to 3.1-point reduction in IQ. Similar significant correlations were observed between IQ and mean lifetime Phe level for early-treated patients (r = 0.34; 95% CI: À0.42 to À0.25), where each 100 lmol/l increase in Phe predicted a 1.9-to 4.1-point reduction in IQ. Moderate correlations were found between concurrent Phe level and IQ for early-treated patients. In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials.
The complete European guidelines on phenylketonuria: diagnosis and treatment
Orphanet Journal of Rare Diseases, 2017
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 Delphimethod 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.
Phenylketonuria in adulthood: a collaborative study
Journal of inherited metabolic disease, 2002
During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjec...
Adults with untreated phenylketonuria: out of sight, out of mind
The British Journal of Psychiatry, 2008
Phenylketonuria is a recessively inherited metabolic disorder which, unless it is treated early enough with a phenylalaninerestricted diet, leads to severe intellectual disabilities. The overall prevalence of phenylketonuria in the UK is about 1 per 10 000 2 and published guidelines suggest that treatment needs to be early and lifelong. Neonatal newborn screening for phenylketonuria began in the late 1960s and those treated early had a very good outcome. 1 However, those born before neonatal screening began were not normally treated, as they already had severe intellectual disabilities, assumed to be irreversible. Our study aimed to trace all those with untreated phenylketonuria and severe intellectual disabilities in the UK and to examine their range of difficulties, as a prelude to a randomised controlled trial of phenylalanine-restricted diet in people with previously untreated phenylketonuria.
Follow up of phenylketonuria patients
Molecular Genetics and Metabolism, 2011
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 lifelong 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 2 years 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.