Dietary protein restriction and provision of adequate non-protein energy are essential components of treatment for urea cycle disorders (UCDs). However, intercurrent illness, stress, injury, surgery, or prolonged fasting can trigger catabolism, leading to increased ammonia concentrations. Unless immediate intervention with reversal of catabolism and reduction of plasma ammonia are undertaken, individuals with UCDs are at risk for hyperammonemic crises that can result in cerebral edema, neurological injury, and potentially death. Outcomes are therefore dependent on early diagnosis and treatment initiation, appropriate management during catabolic events, and consistent treatment and monitoring to maintain metabolic stability, support growth, and promote overall health.

Lack of appropriate nutrition management can result in negative consequences. This may occur when only some recommendations are implemented, when biochemical and clinical outcomes are not monitored, or when nutrient prescriptions are not adjusted (e.g., in response to growth, illness, or other metabolic stressors).

• Excessive protein intake can increase ammonia concentrations, precipitate metabolic decompensation, and negatively impact the central nervous system.
• Over-restriction of protein can result in negative nitrogen balance, essential amino acid deficiencies, impaired growth, sarcopenia, and poor overall outcomes. Chronic dietary restriction may also contribute to subtle micronutrient inadequacies if intake is not routinely assessed and supplemented when indicated. 
• The cumulative burden of lifelong dietary management, frequent monitoring, medication use, and ongoing emergency preparedness may negatively affect quality of life and treatment adherence. 
• Pregnancy in a woman with a UCD involves not only standard UCD management, but also the increased metabolic demands of pregnancy, the health of the fetus, the management of pregnancy-related illness, and the rapid metabolic shifts that occur postpartum, all of which increase risk for hyperammonemia.
• During illness or metabolic stress, catabolism increases endogenous ammonia production and places the individual at high risk for metabolic decompensation.
• Liver transplantation may allow an individual with UCD to consume an unrestricted diet, but without appropriate nutritional counseling and monitoring during the transition, nutrient needs may not be met.
• Implementation of these recommendations may also be limited by inequities in access to care, including the cost and availability of medical foods, insurance coverage, geographic access to metabolic centers, and availability of clinicians with expertise in inherited metabolic disorders.

• Implementing the recommendations would:
• Reduce variations in clinical practice and services across medical centers
• Guide practice decisions that integrate medical and nutrition management
• Provide clinicians with criteria to make recommendations for protein, energy, amino acid supplementation, and monitoring
• Support individualized nutrition care based on the UCD subtype, disease severity, and life stage
• Improve patient outcomes and clinician effectiveness
• Enhance patient quality of life, prevent hyperammonemic crises and long-term neurological complications, and reduce associated medical, educational, and social costs