Nutrition management of PKU with pegvaliase therapy: update of the web-based PKU nutrition management guideline recommendations.

BACKGROUND: The web-based GMDI/SERN PKU Nutrition Management Guideline, published before approval of pegvaliase pharmacotherapy, offers guidance for nutrition management of individuals with phenylketonuria (PKU) treated with dietary therapy and/or sapropterin. An update of this guideline aims to provide recommendations that improve clinical outcomes and promote consistency and best practice in the nutrition management of individuals with PKU receiving pegvaliase therapy. Methodology includes: formulation of a research question; review, critical appraisal, and abstraction of peer-reviewed studies and unpublished practice literature; expert input through Delphi surveys and a Nominal Group process; and external review by metabolic experts. RESULTS: Recommendations, summary statements, and strength of evidence are included for each of the following topics: (1) initiating a pegvaliase response trial, (2) monitoring therapy response and nutritional status, (3) managing pegvaliase treatment after response to therapy, (4) education and support for optimal nutrition with pegvaliase therapy, and (5) pegvaliase therapy during pregnancy, lactation, and adolescence. Findings, supported by evidence and consensus, provide guidance for nutrition management of individuals receiving pegvaliase therapy for PKU. Recommendations focus on nutrition management by clinicians, as well as the challenges for individuals with PKU as a result of therapy changes. CONCLUSIONS: Successful pegvaliase therapy allows the possibility for individuals with PKU to consume an unrestricted diet while still maintaining the benefits of blood phenylalanine control. This necessitates a perspective change in education and support provided to individuals in order to achieve healthy nutrient intake that supports optimal nutritional status. The updated guideline, and companion Toolkit for practical implementation of recommendations, is web-based, allowing for utilization by health care providers, researchers, and collaborators who advocate and care for individuals with PKU. These guidelines are meant to be followed always taking into account the provider's clinical judgement and considering the individual's specific circumstances. Open access is available at the Genetic Metabolic Dietitians International ( https://GMDI.org ) and Southeast Regional Genetics Network ( https://managementguidelines.net ) websites.

Updated, web-based nutrition management guideline for PKU: An evidence and consensus based approach.

BACKGROUND: In 2014, recommendations for the nutrition management of phenylalanine hydroxylase deficiency were published as a companion to the concurrently published American College of Medical Genetics and Genomics guideline for the medical treatment of phenylketonuria (PKU). These were developed primarily from a summary of findings from the PKU scientific review conference sponsored by the National Institutes of Health and Agency for Healthcare Research & Quality along with additional systematic literature review. Since that time, the Genetic Metabolic Dietitians International and the Southeast Regional Newborn Screening and Genetics Collaborative have partnered to create a web-based technology platform for the update and development of nutrition management guidelines for inherited metabolic disorders. OBJECTIVE: The purpose of this PKU guideline is to establish harmonization in treatment and monitoring, to guide the integration of nutrition therapy in the medical management of PKU, and to improve outcomes (nutritional, cognitive, and developmental) for individuals with PKU in all life stages while reducing associated medical, educational, and social costs. METHODS: Six research questions critical to PKU nutrition management were formulated to support guideline development: Review, critical appraisal, and abstraction of peer-reviewed studies and unpublished practice literature, along with expert Delphi survey feedback, nominal group process, and external review from metabolic physicians and dietitians were utilized for development of recommendations relevant to each question. Recommendations address nutrient intake, including updated protein requirements, optimal blood phenylalanine concentrations, nutrition interventions, monitoring parameters specific to life stages, adjunct therapies, and pregnancy and lactation. Recommendations were graded using a rigorous system derived from the Academy of Nutrition and Dietetics. RESULTS AND CONCLUSION: These guidelines, updated utilizing a thorough and systematic approach to literature analysis and national consensus process, are now easily accessible to the global community via the newly developed digital platform. For additional details on specific topics, readers are encouraged to review materials on the online portal: https://GMDI.org/.

The role of evidence analysts in creating nutrition management guidelines for inherited metabolic disorders.

RATIONALE, AIMS AND OBJECTIVES: Evidence and consensus-based guidelines for nutrition management of maple syrup urine disease (MSUD) were developed as part of a project to create nutrition guidelines for inherited metabolic disorders identified through newborn screening. The objective of this study was to describe and evaluate the role of evidence analysts in the systematic review phase of guideline development to improve quality of process and output and inform future guideline development projects. METHODS: Recruitment, training and output of evidence analysts were documented throughout the MSUD project. The role of analysts was to critically review and rate the scientific quality of published literature and abstract pertinent information using quality checklists and abstraction worksheets. A secure, web-based application was developed to standardize the process and establish permanent documentation. Analysts completed a post-project survey on perceptions of their role, training and the evidence analysis process. RESULTS: Of 23 recruits, 65% (15) completed evidence analyst training; 73% of those (11) participated in the analysis of 98 literature articles. Analysts reviewed a median of four articles (range 1-16) with median productivity of 1.1 articles per month. All analysts surveyed (n = 9) understood their role and agreed that training was adequate; 100% agreed that analyst involvement was critical in developing guidelines for MSUD. CONCLUSION: Evidence analysts played a key role in appraising and abstracting evidence to develop nutrition guidelines for MSUD. With critical improvements to the process, particularly more stringent and systematic evaluation and documentation of analyst performance related to productivity and quality, we will continue to recruit, train and support evidence analysts in evidence-based guideline development projects.

Nutrition management guideline for maple syrup urine disease: an evidence- and consensus-based approach.

In an effort to increase harmonization of care and enable outcome studies, the Genetic Metabolic Dietitians International (GMDI) and the Southeast Regional Newborn Screening and Genetics Collaborative (SERC) are partnering to develop nutrition management guidelines for inherited metabolic disorders (IMD) using a model combining both evidence- and consensus-based methodology. The first guideline to be completed is for maple syrup urine disease (MSUD). This report describes the methodology used in its development: formulation of five research questions; review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; and expert input through Delphi surveys and a nominal group process. This report includes the summary statements for each research question and the nutrition management recommendations they generated. Each recommendation is followed by a standardized rating based on the strength of the evidence and consensus used. The application of technology to build the infrastructure for this project allowed transparency during development of this guideline and will be a foundation for future guidelines. Online open access of the full, published guideline allows utilization by health care providers, researchers, and collaborators who advise, advocate and care for individuals with MSUD and their families. There will be future updates as warranted by developments in research and clinical practice.

Enhanced interpretation of newborn screening results without analyte cutoff values.

PURPOSE: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. METHODS: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. RESULTS: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. CONCLUSION: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%.

AsktheGeneticist: five years of online experience.

PURPOSE: To identify the genetic informational needs and assess the level of awareness about clinical genetic services among adults who use the internet. METHODS: We created an online service called AsktheGeneticist (http://www.askthegen.org) to answer questions about medical genetics. Since 2003, we have received 4497 questions from every US state and 84 countries/territories. Genetic counselors draft answers to the questions submitted. The questions and answers are next reviewed by clinical geneticists, then organized by topic and uploaded to the site. A link to an online website-user satisfaction survey is e-mailed to the user with a link to their Q&A. RESULTS: Before visiting AsktheGeneticist, 20% (50/247) of survey respondents were unaware that genetic services existed. After visiting our website, 23.5% (58) of survey respondents sought contact with a genetics health care professional, compared with <1% of patients who self-refer to a general genetics clinic (binomial test; P < 0.0001). Website users most often sought information about a known genetic condition in their family and the risk of recurrence. CONCLUSIONS: Our data suggest that the internet can be an effective tool for increasing the awareness of genetic services and identifying genetic informational needs of online adults, as well as for connecting patients with genetic services.