The guidelines for nutrition management and monitoring of UCD treatment are based on the best available evidence, supplemented by survey results and expert opinion. Across nearly all domains, additional clinical data, well-designed prospective studies, and use of patient registries have the potential to strengthen the evidence base and increase the validity of the recommendations. In addition, future research may further evaluate several emerging and understudied areas, including:

Therapeutics and Biomarkers: 

• Development and integration of novel therapies (e.g., enzyme replacement therapy, gene therapy, etc.)
• The clinical utility of routine phenylbutyrate metabolite testing, including target concentrations for assessing medication adherence and toxicity
• In individuals with CPS, the role, durability of response, and predictors of clinical benefit of carglumic acid therapy

Acute and Chronic Nutrition Management:

• The impact of parenteral nutrition solutions with higher branched-chain amino acid (BCAA) content for protein reintroduction during acute hyperammonemic crises
• Comparative effectiveness of intact protein and essential amino acid-based medical food in children and adults on metabolic control, body composition, nutritional status, and quality of life
• The effect of exercise type, intensity, and timing on metabolic stability, body composition, and total protein tolerance

Reproductive Lifecycle

• The effect of puberty and menses on metabolic stability
• Total protein goals and the proportion of total protein as EAAs necessary to optimize metabolic control and meet maternal and fetal nutrient requirements throughout pregnancy
• Nutritional management and monitoring during the postpartum period and lactation, including protein needs and prevention of catabolism
• Protein requirements in women during peri-menopause and menopause

Considerations for Aging and Bone Health

• Strategies to prevent or mitigate sarcopenia in aging adults with UCDs
• Bone health across the lifespan, including characterization of bone mineral density in individuals with UCDs, optimal screening strategies, and interventions to prevent low bone mineral density

Care Delivery 

• Innovative models of care, including artificial intelligence, home-based ammonia monitoring, remote support, and personalized nutrition tools for individuals with UCDs and providers to improve early intervention, self-management, adherence, and long-term outcomes
• Best practices and relevant outcome measures for care transitions and long-term models of care, including transition from pediatric to adult services, transfer of self-management responsibilities, care coordination across settings, and long-term survivorship in individuals with UCDs