March 2017, v.1.2
Updated: September 2017
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 Clinical Symptoms and Laboratory Findings in PROP
- T.2 Nutrition Problem Identification for PROP based on the Academy of Nutrition and Dietetics Nutrition Care Process
- T.3 Recommended Intakes of PRO and Energy for Well Individuals with PROP
- T.4 Classification of Medical Foods for the Nutrition Management of PROP
- T.5 Nutrient Sources in the Nutrition Management of Well Individuals with PROP
- T.6 Nutrition Management of Individuals with PROP
- T.7 Monitoring the Nutritional Management of Well/Stable Individuals with PROP
- References
- Contributors
- Appendix A: Recommendation Rating Definitions
- Appendix B: Terms
- Disclaimer
Laboratory Test or Clinical Symptoms | Symptomatic / Metabolic Crisis1 | Pre-symptomatic / Treated |
C3 Acylcarnitine on Newborn Screening | ↑ or ↑↑ (confirmatory testing required) | ↑ (confirmatory testing required) |
Plasma amino acids | NL or ↑ GLY, ALA | NL or ↑ GLY, ↑ ALA, ↓ILE2, ↓VAL2 |
Free carnitine | ↓↓ | NL or ↓ |
Metabolic acidosis | ++ | +/− |
Serum glucose | ↓ | NL or slight ↓ |
Serum NH3 | ↑ to ↑↑ | NL or slight ↑ |
Urine organic acids: 3-OH propionate, methylcitrate, propionyl glycine, tiglylglycine | ↑ | NL or slight ↑ |
Lactic acid | ↑ | NL or slight ↑ |
Urine ketones | +++ | NL or slight ↑ |
Cytopenia | + | +/− |
Vomiting | ++ | − |
Poor feeding | ++ | +/− |
Lethargy | ++ | +/− |
Neurologic symptoms (e.g. seizures, hypotonia, dystonia) | ++ | +/− |
Intellectual disability, developmental regression 3 | ++ | +/- |
Impaired growth2 | ++ | +/- |
Cardiomyopathy3 | ++ | +/- |
Pancreatitis3 | +/− | +/- |
1 A neonate detected through NBS may or may not be symptomatic.
2 ILE and/or VAL may be low if intact protein is over-restricted or if excessive medical food protein is provided in the diet.
3 These symptoms/complications are not seen in a newborn with PROP, but may be seen in older individuals, even those who appear to have been well-treated.
Nutrition Diagnosis (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 Excessive protein intake Insufficient protein intake Intake of types of protein or amino acids inconsistent with needs (specify) Predicted excessive energy intake Predicted suboptimal energy intake Excessive fat intake Inadequate fat intake Excessive enteral nutrition infusion Inadequate enteral nutrition infusion Enteral nutrition composition inconsistent with needs 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 | Consumption Factors Lack of medical food consumption Suboptimal medical food consumption Excessive intake of (specify food or beverage) Provider Factors Nutrition prescription no longer meets protein needs Nutrition prescription no longer meets energy needs Underlying Disease Factors New diagnosis of PROP Restriction of propiogenic amino acids (VAL, ILE, MET, and THR) necessary for PROP 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 dietary therapy recommendations Presentation to clinic for initial nutrition education Off diet Access Factors Lack of financial resources for medical food and low-protein foods Lack of medical insurance Inadequate third-party or denial of coverage for medical foods or low protein foods Lack of access to resources or care | From Biochemical Tests Laboratory value compared to norm or goal (specify) (e.g. plasma LEU of 300 µmol/L) Abnormal plasma amino acids (specify) Presence of ketones in urine 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 PROP micronutrient 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) 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 |
Table content is based on Nutrition Care Process (NCP) terminology developed by the Academy of Nutrition and Dietetics (eNCPT. 2016 edition). 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 PROP 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.
AGE/STAGE | Intact PRO 1,2 (g/kg/d) | Total PRO3,4 (g/kg/d) | ENERGY5 (kcal/kg/d) |
0 - 6 mo | 0.91 - 1.52 | 1.52 - 1.82 | M: 72 - 109 F: 72 - 108 |
7 - 12 mo | 0.72 - 1.2 | 1.2 - 1.44 | M: 65 - 97 F: 64 - 96 |
1 - 3 yr | 0.63 - 1.05 | 1.05 - 1.26 | M: 66 - 99 F: 66 - 99 |
4 - 8 yr | 0.57 - 0.95 | 0.95-1.14 | M: 59 - 88 F: 56 - 84 |
9 - 13 yr | 0.57 - 0.95 | 0.95-1.14 | M: 43 - 65 F: 39 - 58 |
14 - 18 yr | 0.51 - 0.85 | 0.85 - 1.02 | M: 36 - 53 F: 30 - 45 |
19 - >70 yr | 0.48 - 0.8 | 0.8 - 0.96 | Varies6 |
Pregnancy 7,8,9 >18yr-50yr | 0.66-1.1 | 1.1-1.32 | Varies10 |
Lactation 11 | 0.78-1.3 | 1.3-1.56 | Varies12 |
- PROP Recommendation 1.1; Provide 60-100% AI/RDA of total protein requirement from complete (intact) protein. Calculated from Y.15: 2002/2005 US DRI for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids (Macronutrients) Food and Nutrition Board Institute of Medicine, The National Academies Press, Washington D.C. pages 619-662.
- PROP Question 2. Diet prescription should be guided by age appropriate DRIs and actual intake adjusted based on patient tolerance, anthropometric and lab monitoring.
- PROP Recommendation 1.2. If less than 100% of AI/RDA from complete protein is tolerated, add PROP medical food to provide 100-120% of AI/RDA for total PRO. Calculated from Y.15.
- PROP Recommendation 1.3 and 1.4. Amino acid profiles differ between sources of intact protein and PROP medical foods.
- PROP Recommendation 1.5. Provide 80-120% total energy requirements. DRI EER calculated with average weight per age group from Y.15 pages 169-178;except for 19-70 yr old and Pregnancy and Lactation groups.
- PROP Guideline Nutrition Recommendation 1.5. For adults individualize 80-120% DRI EER calculations in Y.15 page 183-185.
- PROP Question 5. Women < 19 years of age and women having multiple births have higher nutrient requirements (Source: Y.14 Dietary Reference Intake for Pregnancy Institute of Medicine 2006 https://www.ncbi.nlm.nih.gov/books/NBK32812)
- PROP Question 5. Women may need to adjust their current intake to meet appropriate plasma amino acid levels if their diet was not being strictly followed at the time of conception. PRO and energy needs begin to increase toward the end of the first trimester (Source: Y.14)
- PROP Recommendation 5.1-5.3. There is limited evidence for nutrition management of PROP in pregnancy and lactation.
- PROP Question 5. Energy requirements for pregnancy when BMI is in normal range: Trimester 1- same as pre-pregnancy; Trimester 2: additional 340 kcal/d; Trimester 3 additional 452 kcal (Source: Y.14)
- PROP Question 5. If the individual with PROP is not breastfeeding, return to pre-pregnancy intake. (Source: Y.14)
- PROP Question 5. Energy needs during lactation- same as Trimester 3 (Source: Y.14)
Classification1 | Complete2 | Incomplete (Lower fat and/or carbohydrate) |
Nutrient Profile3 | Amino acids, fats, carbohydrates, vitamins and minerals, L-carnitine | |
Pro:Energy ratio (PRO g/100 kcal)4 | Low to medium | Medium to high |
Forms | Powder | Powder, gel, ready to drink |
Products designed for infants | MMA/PA Anamix Early Years5 Propimex-16 OA-17 | N/A |
Products designed for children | MMA/PA Anamix Next5 Propimex-26 OA-27 | Maxamaid XMTVI5 MMA/PA Gel8,9 MMA/PA Express8,10 MMA/PA Cooler 158,10 Promactin AA plus11 |
Products designed for adults | Propimex-27 OA-27 | Maxamum XMTVI5 MMA/PA Cooler 158,10 Promactin AA plus11 |
1. Examples of products available in the U.S. as of January 2017. Inclusion in table does not represent endorsement
2. Contains nutrients necessary to support growth except for the offending amino acids in PROP: VAL, ILE, MET, THR. Additional sources of energy may also be needed. See manufacturers' product information for amino acid and other nutrient content.
3. Medical foods vary with respect to the amount and/or type of amino acids, carbohydrate, fats, vitamins, minerals, and L-carnitine. See manufacturers information for complete nutrient profile. GMDI members can access a table containing the Nutrient Composition of Medical foods for PROP ( http://gmdi.org/Portals/0/documents/2016%20medicalFoodList%20Group%206%20MMA%20PA.pdf)
4. Energy/Protein ratio categories ((PRO g/100kcal): High: 11-25; Medium 5-10; Low <5
5. Nutricia North America, Gaithersburg, MD
6. Abbott Nutrition, Columbus OH
7. Mead Johnson Nutrition, Evansville IN
8. Vitaflo USA, Alexandria, VA
9. Intended for ages 1-10 years
10. Intended for ages 3 years-adult
11. Cambrooke Therapeutics, Ayer, MA
Nutrient | Recommendation | Source |
|---|---|---|
Intact PRO, ILE, VAL, MET, THR1 | Sufficient PRO intake to allow adequate protein synthesis for growth, repair and health maintenance and to achieve ILE, VAL, MET, THR levels in recommended treatment range. Intact PRO allowance is also dependent on residual PROP enzyme activity, age, weight, sex, life stage and health of the individual with PROP. |
In infants: breast milk or infant formula with known PRO, ILE, VAL, MET, THR content In children and adults : foods such as fruits/vegetables, some grains/cereals, and polymeric formulas for which there is known PRO, ILE, VAL, MET, THR content |
Total PRO, ILE, THR2 | If <100% of intact PRO is tolerated, add PROP medical food to provide total PRO to meet 120% AI/RDA total PRO |
|
KCAL | 80-120% DRI EER3 |
|
Other nutrients, minerals and vitamins6 | DRI 1 |
|
1. For age, size, sex, and life stage PROP Question 1 see Table TABLE #3, Recommended Intakes of PRO and Energy for Well Individuals with PROP. Requirements change with catabolic illness/conditions PROP Question 2
2. PROP Question 1 Recommendation 1.2. Be aware that PROP Medical foods marketed in North America as of Jan 25, 2017 do not contain VAL or MET, but some PROP medical foods contain varying amounts of ILE and THR and carnitine. See Table TABLE #4, Classification of Medical Foods for the Nutrition Management of PROP
3. PROP Question 1 Recommendation 1.5. See Table TABLE #3, Recommended Intakes of PRO and Energy for Well Individuals with PROP
4. Free foods contain little or no detectable PRO/ILE,VAL,MET,THR and consist mostly of sugars, pure starches and/or fats
5. Modified low-protein foods include pastas and baked goods where higher protein grains/flours are replaced by protein-free starches
6. Included are essential fatty acids and DHA, Vit D, Vit A, Ca, Fe, Zn, Se
7. Most PROP medical foods are supplemented sufficiently with the nutrients and micronutrients that may be deficient in a diet restricted in Intact PRO and therefore ILE, VAL, MET, THR. Compliance with taking the full medical food prescription is important in meeting these nutrient requirements. In addition, there are some PROP medical foods that have been modified to improve taste, decrease KCAL or volume in order to increase compliance that may have insufficient supplementation of some micronutrients, vitamins and minerals
Recommendation Key Points1 | Evidence from Topics |
During Acute illness or first presentation | |
Provide aggressive nutritional management (2.1) |
* Adjustments needed if individual is dialyzed |
Protein intake (2.2) |
|
Parenteral Nutrition support (2.3) |
|
Enteral Nutrition Support (2.4) |
|
For Ongoing Management | |
Do not allow extended fasting periods (2.4) |
|
Promote oral intake to develop feeding skills (2.5) |
|
For metabolically stable individuals (2.6) |
|
Home sick day plan Initiate and maintain contact with metabolic clinic as directed | |
Provide an individualized sick day home feeding plan (2.7) |
|
The individuals plan (2.7) |
|
Additional considerations (2.7) |
|
Factors to consider regarding the appropriateness of managing the mildly ill individual at home (2.7) |
|
1 Key Points are derived from Nutrition Recommendations listed in parenthesis.
Domain Measures1 | Infants | Children | Adults | Pregnancy and Postpartum Period | ||
(0-1 year) | (1-7 years) | (8-18 years) | Adults | Pregnancy | Postpartum/ lactation | |
Clinical Assessment | ||||||
Nutrition Visit in Clinic2 dietary intake3and nutrient analysis, nutrition-related physical findings, feeding skills, nutrition counseling, diet education, activity level | Weekly to monthly | Monthly to every 6 months | Every 6-12 months | Every 6-12 months | Monthly to per trimester | At 6 weeks postpartum, then every 6 months while breastfeeding |
Anthropometrics 4 weight, length/ height, weight-for- length, BMI | At every clinic visit3Include head circumference | At every clinic visit3 Include head circumference through 36 months | At every clinic visit | Weight and BMI at every clinic visit | Weight and BMI at every clinic visit | Weight and BMI at every clinic visit |
Developmental, psychomotor function and neurocognitive assessment5 | Neurocognitive testing appropriate for age | |||||
Biochemical (Routine) | ||||||
Amino acids, plasma | Monthly to every 3 months | At every clinic visit or every 6 months | At every clinic visit or every 6 months | At every clinic visit or at least annually | Weekly to monthly | At every clinic visit |
Carnitine: free and acyl, plasma | Monthly to every 3 months | At every clinic visit or every 6 months | At every clinic visit or at least annually | At every clinic visit or at least annually | Weekly to monthly | Every clinic visit |
Ketones, urine (home) | Daily to establish baseline; Weekly; more frequent if clinically unstable | Monthly; Daily when clinically unstable | Monthly; Daily when clinically unstable | Monthly; Daily when clinically unstable | Monthly; Daily when clinically unstable | Monthly; Daily when clinically unstable |
Transthyretin (prealbumin) | 6 - 12 months | 6 - 12 months | 6 - 12 months | At every clinic visit or at least annually | Monthly to per trimester | Monthly |
Albumin/total protein | 6 - 12 months | 6 - 12 months | Yearly | At every clinic visit or at least annually | Per trimester | Yearly |
Complete blood count/differential | 6 - 12 months | Yearly | Yearly | Yearly | Per trimester | Yearly |
Vitamin D25-OH | NA | Yearly | Yearly | Yearly | Per trimester | Yearly |
Biochemical (Conditional) 6 | ||||||
Ammonia7 | Baseline, then every 3-6 months in established patients | Every 3-6 months | Every 6 months | Every 6 months | Baseline | As Indicated |
Comprehensive metabolic panel, serum vitamin B12 , B6, erythrocyte folate, ferritin, zinc, selenium, essential fatty acids | Yearly or as indicatede | Yearly or as indicatede | Yearly or as indicatede | Yearly or as indicatede | At first visit then as indicated | As indicated |
Propionic acid, plasma | Baseline; Every 6 months | Annually, if indicated | Annually, if indicated | Annually, if indicated | At first visit then as indicated | As indicated |
Acylcarnitine profile, plasma | Confirm diagnosis; Every 6 months | Annually, if indicated | Annually, if indicated | Annually, if indicated | As indicated | As indicated |
Organic acids, urine | Confirm diagnosis; Every 6 months | Annually, if indicated | Annually, if indicated | Annually, if indicated | As indicated | As indicated |
Radiological 8 (Conditional) | ||||||
Dual-energy X-ray absorptiometry (DXA) | NA | Every 5 years after age 5 | Every 5 years | Annually | Annually | Annually |
1 Recommendations were derived from literature review, Nominal group and Delphi surveys. Frequency of clinical and laboratory assessments at a metabolic clinic (involving the medical geneticist, metabolic dietitian, social worker, nurse specialist, psychologist, et al.), may not be possible because of travel distance, cost, loss of work days, etc. Coordination with primary care and community-based providers, use of telemedicine, and frequent communication by telephone and mail should be employed. More frequent monitoring may be necessary if individual is not in good metabolic control.
2 Interval nutritional contact between nutritional clinic visits as needed.
3 A mechanism for assessing dietary intake, whenever blood is monitored, should be in place. MetabolicPro ( www.metabolicpro.org) is a computer program available for dietary analysis of amino acid-restricted diets.
4 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 .
5 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 in these areas of medicine.
6 Monitoring is indicated when nutrition assessment indicates poor adherence to diet, inadequate nutrient intake, clinical signs/symptoms of nutritional inadequacy including poor growth, or serious intercurrent illness.
7 Blood ammonia quantification is dependent in part on patient severity and stability. More frequent quantification may be needed to measure effectiveness of use of ammonia-reducing drugs, e.g. carglumic acid. Blood ammonia may not always be a reliable biomarker for assessing patient status, based in part on difficulty in handling of blood specimens.
8 DXA is indicated in individuals who have frequent fractures, and/or low serum 25-hydroxy vitamin D concentrations, or other indices of possible bone abnormalities.