Beth N. Ogata

Phenylketonuria Scientific Review Conference: State of the science and future research needs

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

Recommendations for the nutrition management of phenylalanine hydroxylase deficiency

The effectiveness of a phenylalanine-restricted diet to improve the outcome of individuals with phenylalanine hydroxylase deficiency (OMIM no. 261600) has been recognized since the first patients were treated 60 years ago. However, the treatment regime is complex, costly, and often difficult to maintain for the long term. Improvements and refinements in the diet for phenylalanine hydroxylase deficiency have been made over the years, and adjunctive therapies have proven to be successful for certain patients. Yet evidence-based guidelines for managing phenylalanine hydroxylase deficiency, optimizing outcomes, and addressing all available therapies are lacking. Thus, recommendations for nutrition management were developed using evidence from peer-reviewed publications, gray literature, and consensus surveys. The areas investigated included choice of appropriate medical foods, integration of adjunctive therapies, treatment during pregnancy, monitoring of nutritional and clinical markers, prevention of nutrient deficiencies, providing of access to care, and compliance strategies. This process has not only provided assessment and refinement of current nutrition management and monitoring recommendations but also charted a direction for future studies. This document serves as a companion to the concurrently published American College of Medical Genetics and Genomics guideline for the medical treatment of phenylalanine hydroxylase deficiency.Genet Med 16 2, 121–131.

Position of the Academy of Nutrition and Dietetics: Nutrition Guidance for Healthy Children Ages 2 to 11 Years

It is the position of the Academy of Nutrition and Dietetics that children ages 2 to 11 years should achieve optimal physical and cognitive development, maintain healthy weights, enjoy food, and reduce the risk of chronic disease through appropriate eating habits and participation in regular physical activity. Rapid increases in the prevalence of childhood obesity during the 1980s and 1990s focused attention on young childrens overconsumption of energy-dense, nutrient-poor foods and beverages and lack of physical activity. While recent data suggest a stabilization of obesity rates, several public health concerns remain. These include the most effective ways to promote healthy weights, the number of children living in food insecurity, the under-consumption of key nutrients, and the early development of diet-related risks for chronic diseases, such as cardiovascular disease, type 2 diabetes, cancer, obesity, and osteoporosis. This Position Paper reviews what children 2 to 11 years old in the United States are reportedly eating, explores trends in food and nutrient intakes, and examines the impact of federal nutrition programs on child nutrition. Current dietary recommendations and guidelines for physical activity are also discussed. The roles of parents and caregivers in influencing the development of life-long healthy eating behaviors are highlighted. The Academy of Nutrition and Dietetics works with other allied health and food industry professionals to translate dietary recommendations and guidelines into positive, practical health messages. Specific recommendations and sources of science-based nutrition messages to improve the nutritional well-being of children are provided for food and nutrition practitioners.

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.

Academy of Nutrition and Dietetics: Revised 2017 Scope of Practice for the Registered Dietitian Nutritionist

The Academy of Nutrition and Dietetics (Academy) is the worlds largest organization of food and nutrition professionals and the association that represents credentialed nutrition and dietetics practitioners-registered dietitian nutritionists (RDNs) and nutrition and dietetics technicians, registered (NDTRs). RDNs integrate research, professional development, and practice to stimulate innovation and discovery; collaborate to solve the greatest food and nutrition challenges now and in the future; focus on systemswide impact across the food, wellness, and health sectors; have a global impact in eliminating all forms of malnutrition; and amplify the contribution of nutrition and dietetics practitioners and expand workforce capacity and capability. The Revised 2017 Scope of Practice for the RDN reflects the position of the Academy on the essential role of the RDN in the direction and delivery of food and nutrition services. The scope of practice for the RDN is composed of education and credentialing, practice resources, Academy Standards of Practice and Professional Performance, codes of ethics, accreditation standards, state and federal regulations, national guidelines, and organizational policy and procedures. The Revised 2017 Scope of Practice for the RDN is used in conjunction with the Revised 2017 Standards of Practice (SOP) in Nutrition Care and the Standards of Professional Performance (SOPP) for RDNs. The SOP address activities related to direct patient and client care. The SOPP address behaviors related to the professional role of RDNs. These standards reflect the minimum competent level of nutrition and dietetics practice and professional performance for RDNs. A companion document addresses the scope of practice for the NDTR.

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/.

Academy of Nutrition and Dietetics: Revised 2017 Standards of Practice in Nutrition Care and Standards of Professional Performance for Registered Dietitian Nutritionists

Registered dietitian nutritionists (RDNs) face complex situations every day. Competently addressing the unique needs of each situation and applying standards appropriately are essential to providing safe, timely, patient-/client-/customer-centered, quality nutrition and dietetics care and services. The Academy of Nutrition and Dietetics (Academy) leads the profession by developing standards that can be used by RDNs (who are credentialed by the Commission on Dietetic Registration) for self-evaluation to assess quality of practice and performance. The Standards of Practice reflect the Nutrition Care Process and workflow elements as a method to manage nutrition care activities with patients/clients/populations that include nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention/plan of care, nutrition monitoring and evaluation, and discharge planning and transitions of care. The Standards of Professional Performance consist of six domains of professional performance: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. Within each standard, specific indicators provide measurable action statements that illustrate how the standard can be applied to practice. The Academys Revised 2017 Standards of Practice and Standards of Professional Performance for RDNs, along with the Academys Code of Ethics and the Revised 2017 Scope of Practice for the RDN, provide minimum standards and tools for demonstrating competence and safe practice and are used collectively to gauge and guide an RDNs performance in nutrition and dietetics practice.

Academy of Nutrition and Dietetics: Revised 2015 Standards of Practice and Standards of Professional Performance for Registered Dietitian Nutritionists (Competent, Proficient, and Expert) in Pediatric Nutrition

All of the health care professions recognize that care of infants and children is best managed as a specialty area of practice. Nutrition plays a key role in normal growth and development. Appropriate nutrition care is vital adjuvant therapy for infants and children with acute or chronic illness. Provision of nutrition services in pediatric practice requires that registered dietitian nutritionists (RDNs) have advanced knowledge in the focus area of pediatric nutrition. Therefore, the Pediatric Nutrition Dietetic Practice Group, with guidance from the Academy of Nutrition and Dietetics Quality Management Committee, has developed this revision of the Standards of Practice and Standards of Professional Performance for RDNs in Pediatric Nutrition as a resource for RDNs working in pediatric nutrition to assess skill level and to identify needs for professional development to advance practice in pediatric nutrition. This revision reflects recent advances in pediatric nutrition and replaces the previous Standards published in 2009. The Standards of Practice represent the four steps of the Nutrition Care Process as applied to the care of patients/clients. The Standards of Professional Performance represent six domains of professionalism: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. The Standards of Practice and Standards of Professional Performance are complementary resources for RDNs working in pediatric nutrition and dietetics practice.

Academy of Nutrition and Dietetics: Revised 2017 Scope of Practice for the Nutrition and Dietetics Technician, Registered

The Academy of Nutrition and Dietetics (Academy) is the worlds largest organization of food and nutrition professionals and the association that represents credentialed nutrition and dietetics practitioners-nutrition and dietetics technicians, registered (NDTRs) and registered dietitian nutritionists (RDNs). An NDTRs scope of practice in nutrition and dietetics has flexible boundaries to capture the depth and breadth of the individuals practice. The NDTRs practice expands with advances in many areas, including nutrition, food production, food safety, food systems management, health care, public health, community health, and information and communication technology. The Revised 2017 Scope of Practice for the NDTR reflects the position of the Academy on the essential role of the NDTR in the management and delivery of food and nutrition services. The scope of practice for the NDTR is composed of education and credentialing, practice resources, Academy Standards of Practice and Standards of Professional Performance, codes of ethics, accreditation standards, state and federal regulations, national guidelines, and organizational policy and procedures. The Revised 2017 Scope of Practice for the NDTR is used in conjunction with the Revised 2017 Standards of Practice in Nutrition Care and the Standards of Professional Performance for NDTRs. The Standards of Practice address activities related to direct patient and client care. The Standards of Professional Performance address behaviors related to the technical role of NDTRs. These standards reflect the minimum competent level of nutrition and dietetics practice and professional performance for NDTRs. A companion document addresses the scope of practice for the RDN.

Role of medical food in MMA.

To the Editor: As senior metabolic dietitians who have provided nutritional management for individuals with methylmalonic acidemia (MMA), we wish to comment on the recent article by Manoli et al., “A Critical Reappraisal of Dietary Practices in Methylmalonic Acidemia Raises Concerns About the Safety of Medical Foods. Part 1: Isolated Methymalonic Acidemias”1, published online in this journal in August 2015. This title is misleading because it seems to imply that poor outcomes are due solely to the use of medical foods. We believe that their study does raise some concerns about some of the current management and monitoring practices2 in the context of a complex disease that, in many cases, cannot be optimized by diet alone. Medical food, a term created in 1988 by the Orphan Drug Amendments, is defined as “a food formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation” (http://medpolicy.ibx.com/policies/mpi. nsf/f12d23cb982d59b485257bad00552d87/85256aa800623d 7a85257bf2004f103f!OpenDocument). Although the authors refer to these products as incomplete proteins, they are technically not proteins but, rather, amino acid mixtures that are formulated to minimize the intake of those amino acids that are not catabolized in a specific metabolic disorder, e.g., the propiogenic amino acids in medical foods designed for MMA or propionic acidemia. Medical foods are never intended to be the sole source of nutrient intake for the individual. Limited intake of dietary intact protein (also referred to as natural protein, food protein, or complete protein) is titrated to provide the required essential amino acids, as well as carbohydrates and fat, to provide a nonprotein energy source. The authors suggest that individuals with MMA may be able to meet their protein needs solely with dietary intact protein. However, this overlooks the fact that many individuals with MMA are poor eaters. This may be due in part to chronic acidosis causing anorexia, neurological sequelae that limit the ability to chew and swallow, or aversion to certain textures and tastes. The use of medical foods (in combination with other dietary components containing the propiogenic amino acids) can provide a consistent energy and nutrient source for these poor eaters or for others during intercurrent illness or metabolic crisis. The authors also failed to address the issue of the biological value/quality3 of intact or dietary proteins. Proteins derived from plant sources are less likely to be of high biological value and contain limiting amounts of certain essential amino acids. Moreover, these are the very foods—fruits, vegetables, and some grains—that are the major source of intact dietary protein for individuals with MMA. Reliance solely on these sources can compromise protein status. There are some individuals with milder forms of MMA who can tolerate an intake of intact protein that meets the Dietary Reference Intake for age, but even for these individuals, addition of medical food can provide a “buffer” to allow some leeway in intact protein sources as well as provide an important source of nonprotein energy and micronutrients to meet individual needs. It is important to emphasize that nutritional intervention is not a panacea for the management of individuals with various forms of MMA; these are complex disorders with probable mitochondria dysfunction, chronic renal disease, and risk for decompensation during intercurrent illness. Therefore, it is difficult to equate growth parameters with nutrient intake. The subjects enrolled in this study had diverse nutritional, medical, and supportive interventions and illness histories. Some were identified only after significant decompensation. All of these factors can impact their growth and development, even if they had all followed similar dietary interventions. The authors raise important concerns about practices of increasing total protein intake by giving very large quantities of medical food and the negative impact of elevated leucine intake on the concentration of other essential amino acids. Medical foods available for use by individuals with MMA vary widely in their leucine content, as shown in Supplementary Table S2 online. The composition of some of these products deserves careful reevaluation. Attempts to establish normal plasma amino acid ratios have been shown to improve growth parameters in other inborn errors of metabolism, such as phenylketonuria,4 and may be an important goal for individuals with MMA. Short-term use of intact dietary protein alone may help establish appropriate plasma amino acid ratios, but the data are not available to show the long-term nutritional, anthropometric, and developmental outcomes of omitting medical foods in the management of individuals with MMA. We believe their data suggest that the use of close and frequent monitoring should guide the balance between the amount of medical food amino acids and intact protein in providing the total protein required for adequate growth and maintenance. Even when using amino acids (medical foods) as part of the nitrogen source, total protein intake more than 1.2–1.5 times the Dietary Reference Intake is probably unnecessary. The authors demonstrated this by comparing anthropometric data with total protein intake. If additional energy is needed to promote anabolism, then this should probably come from nonprotein sources, rather than from additional amino acid–based medical food. If plasma levels of valine and isoleucine are low, then additional intact protein sources can be used and an equivalent decrease in amino acids from medical food can be considered. Genet Med