Management
Guidelines
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PROP Nutrition Management Guidelines
First Edition
March 2017, v.1.2
Updated: September 2017
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List of Tables
TABLE #1: Clinical Symptoms and Laboratory Findings in PROP

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.

TABLE #2: Nutrition Problem Identification for PROP based on the Academy of Nutrition and Dietetics Nutrition Care Process

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.

TABLE #3: Recommended Intakes of PRO and Energy for Well Individuals with PROP

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

  1. 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.
  2. PROP Question 2. Diet prescription should be guided by age appropriate DRIs and actual intake adjusted based on patient tolerance, anthropometric and lab monitoring.
  3. 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.
  4. PROP Recommendation 1.3 and 1.4. Amino acid profiles differ between sources of intact protein and PROP medical foods.  
  5. 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.
  6. PROP Guideline Nutrition Recommendation 1.5. For adults individualize 80-120% DRI EER calculations in Y.15 page 183-185.
  7. 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)
  8. 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)
  9. PROP Recommendation 5.1-5.3. There is limited evidence for nutrition management of PROP in pregnancy and lactation.
  10. 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)
  11. PROP Question 5. If the individual with PROP is not breastfeeding, return to pre-pregnancy intake. (Source: Y.14)
  12. PROP Question 5. Energy needs during lactation- same as Trimester 3 (Source: Y.14)
TABLE #4: Classification of Medical Foods for the Nutrition Management of PROP

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

TABLE #5: Nutrient Sources in the Nutrition Management of Well Individuals with PROP

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.

  • Intact protein (PRO)

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

  • Intact PRO (as above)
  • PROP medical food

KCAL

80-120% DRI EER3

  • Intact PRO
  • PROP medical food
  • Free foods 4
  • Modified low PRO food 5

Other nutrients, minerals and vitamins6

DRI 1

  • Intact PRO
  • PROP medical food
  • Supplemental nutrients, vitamins and minerals 7

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

TABLE #6: Nutrition Management of Individuals with PROP

Recommendation Key Points1

Evidence from Topics

During Acute illness or first presentation

Provide aggressive nutritional management (2.1)

  • Fluids& electrolytes @ 1.5 - 2 x maintenance*
  • Energy@ 1.1 - 1.5 x recommended
  • Carnitine @ 100-300 mg/day
  • Insulin; to prevent or reverse hyperglycemia
* Adjustments needed if individual is dialyzed

Protein intake (2.2)

  • Withhold no longer than 12 - 48 hours
  • Re-introduce @ 0.5 - < 0.75gm/kg/day with complete protein
  • Increase by 0.25 - <0.5 gm/kg/day

Parenteral Nutrition support (2.3)

  • Administer 10% dextrose IV @ age-dependent glucose requirements to maintain blood glucose at 120-170 mg/dL (and insulin if needed)
  • Add 20% IV lipid @ 2 gm/kg/day
  • Start with standard IV amino acid solution as per 2.2 Protein intake
  • Use propiogenic-free amino acid TPN solution when protein DRI cannot be tolerated from standard IV amino acid solution during times when prolonged bowel rest is needed

Enteral Nutrition Support (2.4)

  • Supplement oral intake & administer medications
  • Reduce number of hours fasting via overnight feedings or more frequent daytime feedings
  • Provide nutritional support when with anorexia due to poor metabolic control
  • Use propiogenic-free amino acid medical food when protein DRI cannot be tolerated from complete protein source

For Ongoing Management

Do not allow extended fasting periods (2.4)

  • Should not exceed 4-6 hours for infants (≤12 months of age)
  • Should not exceed 8 hours after infancy (>12 months of age)

Promote oral intake to develop feeding skills (2.5)

  • Use adaptive/assistive feeding devises
  • Provide extra attention and encouragement
  • Use behavioral intervention and positive reinforcement and guidance techniques to address refusal, gagging, and vomiting and delays in feeding skills

For metabolically stable individuals (2.6)

  • Meet nutrient requirements listed in Q#1 (see Table 1.1)
  • Adjustment of intake for individual tolerance, growth spurts and minor illnesses
  • Despite the lack of evidence, dietary odd-chain fatty acid restriction can be considered

Home sick day plan

Initiate and maintain contact with metabolic clinic as directed

Provide an individualized sick day home feeding plan (2.7)

  • With mild illnesses without GI symptoms
  • When urinary ketones are small or less

The individuals plan (2.7)

  • Consider reduction of total protein from complete protein and medical food for 24 - 48 hours
  • Increase energy intake from carbohydrates / fats
  • Maintain hydration
  • Monitor clinical signs and symptoms

Additional considerations (2.7)

  • Administer more frequent feedings with smaller volumes to aid enteral tolerance
  • Restriction of complete protein should not exceed 48 hours

Factors to consider regarding the appropriateness of managing the mildly ill individual at home (2.7)

  • Patient's age
  • Severity of illness
  • Distance to clinic
  • Caregiver's ability to accurately report, monitor and manage
  • History of previous illnesses and outcomes

1 Key Points are derived from Nutrition Recommendations listed in parenthesis.

TABLE #7: Monitoring the Nutritional Management of Well/Stable Individuals with PROP

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.

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