Are Carriers Unaffected? A Literature Review of Metabolic and Health Outcomes among Genetic Carriers of Phenylketonuria.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive genetic condition that results in reduced enzymatic functioning within the phenylalanine hydroxylase (PAH) pathway, which is involved in the metabolism of phenylalanine (Phe) into tyrosine (Tyr). Without dietary intervention, individuals with PKU exhibit significantly elevated levels of Phe, which is presumed to cause severe neurological dysfunction and other associated health risks. Carriers of PKU are heterozygotes for a PAH gene mutation and are typically described in the literature as "unaffected." However, decades of existing research challenges this classical thinking and it is plausible that these individuals currently classified as carriers may present with an intermediate phenotype or may be "moderately affected." SUMMARY: The purpose of this scoping review was to explore this hypothesis further, by searching for and summarizing existing literature on metabolism and health outcomes among PKU carriers. Preliminary research has suggested that some PKU carriers exhibit reduced PAH enzyme function, and relatedly, elevated circulating Phe levels compared to noncarriers. In addition, Phe dosing trials have further demonstrated that carriers have increased Phe levels and decreased Tyr levels compared to noncarriers. Because of these metabolic perturbations, it is biologically plausible for carriers to experience an intermediate phenotype in terms of metabolic consequences and clinical outcomes. While these outcomes have yet to be thoroughly explored, early research has found associations between PKU carrier status and lower IQs as well as decreased executive functioning, memory, processing speed, and inhibitory control. The PAH pathway is also involved in melanogenesis, and research has demonstrated increased melanoma risk among PKU carriers. However, there are many limitations to this research, and thus whether or not carriers are clinically impacted cannot yet be conclusively determined. KEY MESSAGE: Overall, while preliminary research suggests a possible intermediate phenotype among PKU carriers, the current available research is limited and PKU carriers are still clinically considered "unaffected." This review outlines the current literature while discussing future research endeavors related to the metabolism and health of PKU carriers.

Modified Delphi Process to Identify Research Priorities and Measures for Adult Lifestyle Programs to Address Type 2 Diabetes and Other Cardiometabolic Risk Conditions.

OBJECTIVES: Clinical and community guidelines recommend lifestyle (i.e. diet and physical activity) interventions for cardiometabolic conditions (including type 2 diabetes), yet current evidence suggests limited and variable services in primary care and public health settings. New implementation research studies are needed to ensure maximal effectiveness, equity and efficiency across all population subgroups and within the context of health systems. Such work will benefit from use of similar core measures and outcome indicators across studies. This Delphi process was undertaken by a new interdisciplinary volunteer researcher network to identify research priorities and core measures for such studies. METHODS: Interested network members completed 2 rounds of a modified Delphi process delivered through online questionnaire and teleconferences. Consensus was defined as the median and interquartile range within the top third of a 9-point scale. RESULTS: Twenty-five of 53 (47%) members and 18 (34%) participants completed the round 1 and round 2 surveys, respectively. Of 22 possible research priorities, 4 were rated high priority with consensus, including evaluating the efficacy and effectiveness of interventions in place, improving existing interventions for sustainability and clinical and public health research to advance existing knowledge to develop new capacities. Only 15 of the 93 measures and indicators proposed achieved similar consensus. CONCLUSIONS: This first effort confirms broad agreement on research priorities and limited agreement on core indicators/measures. The results provide a starting point for further development of common measures for implementation research in lifestyle studies addressing cardiometabolic conditions.

Towards a Standardized Definition of Medical Nutrition Therapy and Regulatory Reform in Canada.

Various definitions have been proposed to describe Medical Nutrition Therapy (MNT). Broadly, MNT encompasses the provision of nutrition information and advice aimed to prevent, treat, and/or manage health conditions. In Canada, the provision of such information and advice is unregulated, thus allowing anyone to provide MNT services regardless of their education and training. This inevitably poses risks of harm such as the provision of unsafe and/or ineffective nutrition advice as well as delayed evidence-based treatment. Canadian research has further demonstrated that the general public is unable to properly differentiate between regulated, evidence-based nutrition providers (registered dietitians) and those who are unregulated. Therefore, the public is at risk. To reduce nutrition misinformation and ultimately improve the health and well-being of the public, the objective of this paper is, first, to propose a standardized definition of MNT for use across Canada and, second, to propose province- and territory-specific legislative amendments for the regulation of MNT throughout the country. We also present an opposing perspective to the proposed viewpoint. Ultimately, health care regulation across the country requires an overhaul before we expect that nutrition information and advice communicated to the public may be consistently evidence based.