April 2026, v.1.2
Updated: April 2026
Feedback/Comments :: View Release Notes
- Overview
- Methodology
- Background
- Biochemical Pathway and Nutrition Treatment Rationale
- Nutrition Assessment
- Comparative Standards
- Nutrition Problem Identification
- Nutrition Intervention
- Nutrition Recommendations
- Monitoring and Evaluation
- Resources
- Benefits and Harms of Implementing the Recommendations
- Barriers to Implementation
- Areas for Future Research
- List of Tables
-
Literature Evidence Summary Tables
- T.1 Total Protein and Energy Recommendations for Individuals with Urea Cycle Disorders When Well
- T.2 Monitoring the Nutritional Management of an Individual with UCD when Well
- T.3 Genetic Basis of Urea Cycle Disorders and Related Disorders
- T.4 Nutrition Problem Identification for UCDs
- References
- Contributors
- Appendix A: Recommendation Rating Definitions
- Appendix B: Terms
- Disclaimer
| Disorder | Life Stage | Total Protein, g/kg/d 1,2,3 | Protein DRI for Healthy Individuals, g/kg/day | Essential Amino Acid-Based Medical Food | Individual Amino Acid Supplementation4 | Energy (%DRI) |
|---|---|---|---|---|---|---|
| CPS, OTC5, CIT-I, ASA, ARG6 | 0-12 months | 1.1-2.2 | 1.52 (0-6 m) 1.2 (7-12 m) | Severe phenotype Provides up to 50% of total protein7 Mild phenotype Usually not required | CPS and OTC: L-citrulline (100-200 mg/kg/day) CIT-I and ASA: L-arginine 100-300 mg/kg/day if <20 kg or 2.5-6 g/m²/day if > 20 kg ARG: Avoid L-arginine | 100-120% |
| 1-8 years | 1.0-1.5 | 1.05 (1-3 yr) 0.95 (4-8 yr) | 100% | |||
| 9-18 years | 0.8-1.4 | 0.95 (9-13 yr) 0.85 (14-18 yr) | ||||
| >18 years | 0.7-1.0 | 0.80 | ||||
| Pregnancy | start with pre-pregnancy tolerance8 | 1.1 (or an additional 25 g protein/day) | ||||
| Postpartum | pre-pregnancy tolerance9 | If lactating: 1.3 (or additional 25 g protein /day) | 100-120% |
Abbreviations: DRI, Dietary Reference Intakes; EAA, essential amino acid
- Represents total protein intake (i.e., intact protein plus EAA medical food).
- Individual protein needs may fall out of the recommended ranges to achieve optimal outcomes.
- For individuals with severe UCD phenotype, begin at the lower end of the range and monitor tolerance (ensure adequate plasma amino acids and growth while maintaining normal glutamine and ammonia).
- L-citrulline and L-arginine supplementation is typically administered in divided daily doses, with dosing adjusted based on biochemical and clinical monitoring.
- Includes symptomatic OTC heterozygotes.
- Protein tolerance in individuals with ARG is often at the lower end of recommended ranges.
- Example for an infant receiving 50% of total protein as EAA medical food: total protein=1.0 g protein/kg; 0.5 g/kg provided as intact protein and 0.5 g/kg as EAA medical food.
- Protein tolerance varies and generally increases in the 2nd and 3rd trimesters; see Recommendation 7.3.1.
- During lactation, protein tolerance typically exceeds pre-pregnancy tolerance and is often similar to second-third trimester tolerance.
Domain Measures1 | Infants | Children | Adults | Pregnancy and Postpartum | ||
0-12 months | 1-8 years | 9-18 years | ≥18 years | Pregnancy | Postpartum | |
Clinical Assessment | ||||||
Mild UCD: Nutrition Encounter in Clinic (assess and/or analyze nutrient intake2, nutrition-related physical findings, activity level, feeding skills, and provide nutrition counseling) | Every 3 mo | Every 3-6 mo | Every 6 mo | Yearly | Per trimester | Every 2-4 weeks |
Mild UCD: Nutrition Encounter in Clinic (assess and/or analyze nutrient intake2, nutrition-related physical findings, activity level, feeding skills, and provide nutrition counseling) | Every 3 mo | Every 3-6 mo | Every 6 mo | Yearly | Per trimester | Every 2-4 weeks |
Severe UCD: Nutrition Encounter in Clinic (assess and/or analyze nutrient intake2, nutrition-related physical findings, activity level, feeding skills, and provide nutrition counseling) | Every 1-3 mo | Every 3 mo | Every 3-6 mo | Every 6 mo | Monthly to per trimester | At one week then every 1-4 weeks |
Severe UCD: Interim Nutrition Telephone Encounter | Every 1-4 weeks | As indicated | At least every 3 mo | As indicated | Every 1-4 weeks | Every 1-4 weeks |
Anthropometrics3 (weight, length or height, weight-for-length or BMI, head circumference) | At every clinic visit. Include head circumference through 36 months of age. | |||||
Biochemical Assessment (Routine) | ||||||
Plasma amino acids | Every 1-3 mo | Every 3-6 mo | Every 3-6 mo | Every 6-12 mo | Mild UCD: Monthly to per trimester Severe UCD: Every 1-4 weeks | Every clinic visit |
Ammonia4 | As indicated | |||||
Comprehensive metabolic panel (to include albumin, total protein, and liver function tests) | Every clinic visit to once yearly | Monthly to once per trimester | At least once postpartum | |||
Complete blood count | Mild UCD: Once yearly or as indicated Severe UCD: Every clinic visit to once yearly | Per trimester to once during pregnancy | At least once postpartum | |||
25-hydroxy vitamin D | Yearly or as indicated | Per trimester to once during pregnancy | At least once postpartum | |||
Ferritin5 | Yearly or as indicated | Per trimester to once during pregnancy | At least once postpartum | |||
Biochemical Assessment (Conditional) 6 | ||||||
Vitamins, minerals, and/or trace elements (e.g. serum vitamin B12 and/or methylmalonic acid, serum iron, transferrin saturation, total iron-binding capacity, erythrocyte folate, zinc, copper, selenium) | Yearly or as indicated | At first visit and then as indicated | As indicated | |||
Essential fatty acid profile | As indicated | At first visit and then as indicated | As indicated | |||
Coagulation (INR, PT, PTT) | Mild UCD: As indicated Severe UCD: Yearly or as indicated | As indicated | As indicated | |||
Free/total carnitine | As indicated | |||||
Cholesterol/triglycerides | As indicated | |||||
Lipase/amylase | As indicated | |||||
Bone Density Assessment | ||||||
DXA scan7 (Dual-energy X-ray absorptiometry) | N/A | N/A | As indicated | As indicated | N/A | N/A |
Psychological Monitoring | ||||||
Neurocognitive testing8 | As appropriate for age | |||||
Health-related quality of life | Yearly | |||||
1 Recommendations were derived from literature review, Nominal group, and Delphi surveys. Recommended frequency of clinical and laboratory assessments represent practice goals but may not be possible under all clinical circumstances or appropriate for all individuals with a UCD. Clinicians should apply professional judgment in making individualized monitoring choices. Coordination with primary care and community-based providers, use of telemedicine, and frequent communication should also be employed as needed. More frequent monitoring may be necessary if the individual is not in good metabolic control.
2 A mechanism for analyzing dietary intake should be in place whenever blood is monitored. MetabolicPro (www.metabolicpro.org) is a computer program available for dietary analysis of amino acid-restricted diets.
3 The Centers for Disease Control and Prevention (CDC) recommends using the 2006 World Health Organization (WHO) Child Growth Standards to evaluate growth of infants ages birth to 24 months. The CDC recommends using the 2000 CDC Growth Charts (CDC) to evaluate the growth of children ages 2-20 years. Techniques for measurement are described on the CDC website. http://www.cdc.gov/growthcharts/cdc_charts.htm .
4 Blood ammonia quantification is dependent, in part, on individual disease severity and metabolic stability. Blood ammonia may not always be a reliable biomarker for assessing patient status, based in part on difficulty in handling of blood specimens.
5 Ferritin should not be used to assess iron status in individuals with LPI, as it is a non-specific marker of metabolic or inflammatory stress.
6 Monitoring is indicated when: nutrition assessment shows poor adherence to prescribed therapy (diet, medical food, or pharmacotherapy), incomplete medical food is consumed, clinical symptoms of nutritional inadequacy are present (e.g. poor growth), or there is serious intercurrent illness. If laboratory values are abnormal, reassessment of appropriate analytes should be scheduled.
7 DXA is indicated in individuals who have frequent fractures, low serum 25-hydroxy vitamin D concentrations, or other indices of possible bone abnormalities.
8 These are informal global assessments to identify any developmental and psychomotor issues that may influence approach to diet management. Formal assessments for neurocognitive and development should be performed as needed by specialist(s) in these areas of medicine.
Disorder (Abbreviation) | Gene | Enzyme |
Urea Cycle Disorders | ||
Carbamoyl phosphate synthetase deficiency (CPS) | CPS1 | carbamoyl phosphate synthetase I |
Ornithine transcarbamylase deficiency (OTC) | OTC | ornithine transcarbamylase |
Citrullinemia type 1 (CIT-I) | ASS1 | argininosuccinate synthase 1 |
Argininosuccinic aciduria (ASA) | ASL | argininosuccinate lyase |
Argininemia (ARG) | ARG1 | arginase |
Amino acid transporter deficiencies and other disorders that present like UCDs | ||
Carbonic anhydrase VA deficiency (CA-VA) | CA5A | carbonic anhydrase VA |
Citrullinemia type II (CIT-II); and Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) | SLC25A13 | citrin |
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) | SLC25A15 | ornithine transporter 1 |
Lysinuric protein intolerance (LPI) | SLC7A7 | y+L amino acid transporter 1 |
N-acetyl glutamate synthetase deficiency (NAGS) | NAGS | N-acetylglutamate synthase |
Ornithine aminotransferase deficiency (OAT) | OAT | ornithine aminotransferase |
Nutrition Diagnosis1 (Problem) | Related to (Etiology) | As Evidenced By (Signs and Symptoms) |
Based on assessment findings, specify the current nutrition-related problem(s) to be addressed through nutrition management. | Identify the most pertinent underlying cause(s) or contributing risk factors for the specific problem. The etiology is commonly the target of nutrition intervention. | List subjective and objective data that characterize the specific problem and are also used to monitor nutrition intervention and outcomes |
Examples of specific nutrition problems: | Examples of underlying causes of the problem: | Examples of data used to determine and monitor the problem: |
Intake Domain Predicted excessive energy intake Predicted suboptimal energy intake Excessive protein intake Inadequate protein intake Predicted inadequate nutrient intake (specify) Intake of type of protein inconsistent with needs (specify, e.g., excessive low biological quality protein, inadequate EAA or high biological value protein) Inadequate essential amino acid intake Excessive enteral nutrition infusion Inadequate enteral nutrition infusion Enteral nutrition composition inconsistent with needs Excessive duration between feeds (fasting) Clinical Domain Impaired nutrient utilization Altered nutrition-related lab values Food-medication interaction (specify) Growth rate below expected Underweight Overweight/obesity Behavioral-Environmental Domain Food and nutrition-related knowledge deficit Limited adherence to nutrition-related recommendations Limited access to food Limited access to medical food2 | Consumption Factors Lack of medical food2 consumption Suboptimal medical food2 consumption Excessive intake of (specify food or beverage) Inadequate intake of (specify food or beverage) Long duration between feedings Provider Factors Nutrition prescription no longer meets protein needs Nutrition prescription no longer meets energy needs Underlying Disease Factors New diagnosis of (specify UCD subtype) Protein restriction necessary for UCD treatment Acute illness or infection Poor appetite due to (specify) Patient/Caretaker Knowledge and Behavior Factors Food choices suboptimal Lack of knowledge Limited adherence to nutrition-related recommendations Presentation to clinic for initial nutrition education Presentation to clinic for revised nutrition education (specify, e.g., illness, growth, pregnancy) Change in nutrient needs (specify, e.g, energy) due to new or increased physical activity Access Factors Lack of financial resources for medical food2 Lack of medical insurance Inadequate third-party or denial of coverage for medical foods2 Lack of access to resources for care | From Biochemical Tests Laboratory value compared to norm or goal (specify, e.g., plasma glutamine >1000 µmol/L) Abnormal plasma amino acids (specify) From Anthropometrics Growth pattern, weight, weight-for-height or BMI compared to standards (specify) Weight gain/loss (specify weight change) over the past (specify time frame) From Clinical/Medical Exam or History New diagnosis of (specify UCD subtype) Micronutrient deficiency (physical sign or lab value) Essential fatty acid deficiency (physical sign or lab value) From Diet History Estimated or calculated intake from diet record or dietary recall, compared to recommendation or individual's nutrition prescription (specify) Incomplete/inadequate/missing diet history or recall From Patient Report Verbalized lack of skill or understanding to implement nutrition recommendations Lack of appreciation for the importance of making nutrition-related changes Lack of social or familial support |
1Table content is based on Nutrition Care Process (NCP) terminology developed by the Academy of Nutrition and Dietetics. NCP uses the following structure for documenting nutrition problems: nutrition diagnosis (Problem), related to (Etiology), and as evidenced by (Signs and Symptoms). Examples listed identify concerns particular to UCDs and are grouped in domains of: Intake, Clinical, and Behavioral-Environmental. Problems identified may relate to any Etiology and be evidenced by any Signs and Symptoms within a domain.
2Essential amino acid-based medical food.