Phenotype | Clinical Symptoms (prior to treatment) | Biochemical | % BCKD activity |
Classical | Neonatal onset, poor feeding, lethargy, altered tone, ketoacidosis, seizures. Symptoms often present prior to learning NBS results. Prenatal testing in at-risk siblings can allow dietary intervention at birth. Nearly all due to mutations in the E1 BCKD subunits | ↑↑ allo-ILE, BCAA, BCKA | 0 -2 |
Intermediate | Failure to thrive, ketoacidosis and developmental delay; classical symptoms can occur during catabolic illness/stress | ↑ allo-ILE, BCAA, BCKA | 3 - 30 |
Intermittent | Normal early development, episodic ataxia/ketoacidosis, severe symptoms may be precipitated by catabolic illness/stress. May be missed by MS/MS NBS | Normal BCAA, BCKA when asymptomatic | 5 - 20 |
Thiamin (B1) responsive | Similar to intermediate. Often due to mutations in E2 BCKD subunit | ↑ allo-ILE, BCAA, BCKA ↓BCKA and/or BCAA with thiamin therapy | 2 - 40 |
Lipamide dehydrogenase deficiency | Normal neonatal period, failure to thrive, hypotonia, lactic acidosis, developmental delay, movement disorder. Due to mutations in the E3 BCKD subunit - a component of both pyruvate dehydrogenase and α-ketoglutarate dehydrogenase | Moderate BCAA and BCKA, ↑α-ketoglutarate, pyruvate | 0 - 25 |
Laboratory test/symptom | Symptomatic | Pre-symptomatic/treated |
MS/MS NBS on blood spot | ↑↑BCAA, especially LEU; LEU:PHE ratio > 4.5-5 | <24 hr of age : normal or slight ↑BCAA; > 24 hr of age : slight ↑to ↑BCAA Treated in good control: normal or slight ↑BCAA |
Plasma amino acids | ↑↑BCAA (especially LEU), allo-ILE present; without TX, VAL and ILE may become normal or low. As LEU increases, see decreases in other essential and non-essential AA | normal or slight ↑BCAA; allo-ILE present |
Urine DNPH Rx | ++ after day 2-3 of life | - |
Urine organic acid analysis | ↑BCKA | normal or slight ↑ |
Ketonuria (urine keto sticks) | ++ | - |
Ammonia | May be ↑ or ↑↑ | - |
BCKD activity | 0-3% | 0-3% |
Blood glucose | ↓ or normal | normal |
Weight | ↓ | normal |
Lethargy, intermittent apnea, opisthotonus | + | - |
Maple syrup odor (in urine) | + usually by 72+ hr, (first apparent in cerumen by 12-24 hr) | - |
Irritability, poor feeding | + | - |
Vomiting | + | - |
Ataxia | + | - |
Visual hallucinations | + | - |
Coma, respiratory failure by 7-10 days of life without treatment | + | - |
Nutrient | Recommendation | Source |
LEU | Sufficient intake to allow adequate protein synthesis for growth, repair and health maintenance and to achieve LEU levels in recommended treatment range. LEU allowance is also dependent on residual BCKD activity, age, weight, sex, life stage and health of the individual with MSUD. In the newborn, the recommended intake is: 40-100 mg LEU/kg/day |
In infants: breast milk or infant formula with known LEU content In children and adults: foods such as fruits/vegetables, some grains/cereals that are typically low in protein and for which there is known LEU content |
PRO | DRI 1 Plus additional 20-40% if an amino acid-based medical food is used |
|
VAL, ILE | VAL and ILE are essential amino acids and may need to be supplemented when BCAA are restricted to achieve appropriate LEU blood levels. To promote anabolism of LEU, when LEU blood levels are high, additional supplementation of VAL and ILE is often required |
|
KCAL | DRI 1 |
|
Other nutrients, minerals and vitamins 5 | DRI 1 |
|
1 For age, size, sex, and life stage. Requirements change with catabolic illness/conditions
2 1% solutions are convenient for adding to the medical food when supplementation is necessary
3 Free foods contain little or no detectable PRO/BCAA and consist mostly of sugars, pure starches and/or fats
4 Modified low-protein foods include pastas and baked goods where higher protein grains/flours are replaced by protein-free starches
5 Included are essential fatty acids and DHA, Vit D, Vit A, Ca, Fe, Zn, Se
6 Most BCAA-free medical foods are supplemented sufficiently with the nutrients and micronutrients that may be deficient in a diet low in BCAA. Compliance with taking the full medical food prescription is important in meeting these nutrient requirements. In addition, there are some 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
AGE | NUTRIENT | |||||
LEU mg/kg | ILE mg/kg | VAL mg/kg | PROTEIN g/kg | ENERGY kcal/kg | FLUID ml/kg | |
0 to 6 mo | 40-100 | 30-90 | 40-95 | 2.5-3.5 | 95-145 | 125-160 |
6 to 12 mo | 40-75 | 30-70 | 30-80 | 2.5-3.0 | 80-135 | 125-145 |
1-3 yr | 40-70 | 20-70 | 30-70 | 1.5-2.5 | 80-130 | 115-135 |
4-8 yr | 35-65 | 20-30 | 30-50 | 1.3-2.0 | 50-120 | 90-115 |
9-13 yr | 30-60 | 20-30 | 25-40 | 1.2-1.8 | 40-90 | 70-90 |
14-18 yr | 15-50 | 10-30 | 15-30 | 1.2-1.8 | 35-70 | 40-60 |
19 yr + | 15-50 | 10-30 | 15-30 | 1.1-1.7 | 35-45 | 40-50 |
Ref | Trimester | Total protein (g/kg body weight) | Intact protein (g/kg body weight) | BCAA-free protein (g/kg body weight) |
Pre-pregnancy | 1.0 – 1.2 g | 0.6 – 0.8 g | 0.4 g | |
First trimester | 1.2 g | 0.6 g | 0.6 g | |
Second trimester | ~ | 0.8 g1 | ~ | |
Postpartum | ~ | 1.0 g | ~ | |
First trimester | 1.1 g | 0.1 g | 0.9 g | |
Second trimester | 1.5 g | 0.4 g | 1.1 g | |
Third trimester | 1.1 g | 0.4 g | 0.8 g | |
L.8 2 | Lactation | 1.1 g | 0.4 g | 0.8 g |
1 Increased to normalize low plasma BCAA levels: ~ not specified
2 Nutrient requirements during lactation are similar to those of the third trimester
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 MSUD LEU, VAL, and ILE restriction necessary for MSUD 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 Positive DNPH test 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 MSUD EFA 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. 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 MSUD 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.
Findings from Delphi Survey Round 1
Conducted October 2010
METABOLICALLY STABLE INDIVIDUALS WITH MSUD | |||||
Clinical Statement (Item # on survey) | RD % Agreement n=11 | MD % Agreement n=6 | Notable Comments | Discussion Points for Consideration | Agreement Rating (1-7) Mean +/- SD |
Protein Recommendation | |||||
Meeting the age-appropriate DRI for protein (sum of amino acids in medical food and intact protein) is sufficient for individual with classical MSUD (21) | 18 (82% disagree) | 100 | 1 MD and 4 RDs indicated they give more (up to 30%), especially when source is metabolic formula | Large discrepancy between RD and MD | 3.9 +/- 1.9 Low agreement rating |
The protein equivalent in only the medical food should be used to determine adequacy of dietary protein intake of an individual with classical MSUD (22) | 27 (73% disagree) | 0 (100% disagree) | Discrepancy between RD and MD | 2.8 +/- 1.6 Strong disagreement | |
Recommendation for the amount of protein in the diet should be above the DRI when the majority of protein is provided in the form of protein equivalent from free amino acids (23) | 82 | 67 | RD Labs should also be guide | 5.2 +/- 1.6 | |
Recommendation for the amount of protein in the diet should be based on ideal body weight for age (24) | 55 (36% disagree) | 83 (17% disagree) | 6 RDs indicate actual weight used if normal weight range and IBW if underweight | Discrepancy between RD and MD | 4.8 +/- 1.4 Low agreement rating |
Fluid Requirements | |||||
Infants weighting up to 10 kg: 100 ml/kg body weight (25a) | 82 | 83 | 5.6 +/- 1.4 | ||
Children 11-20 kg: 1000 ml + 50 ml for every kg over 10 kg body weight (25bb) | 82 | 83 | 5.6 +/- 0.9 | ||
Children >20 kg: 1500 ml + 50 ml for every kg over 10 kg body weight (25c) | 82 | 67 | 5.2 +/- 1.3 | ||
Adults: 30-45 ml/kg body weight (25d) | 82 | 83 | RD fluid ad lib if eating well and stable | 5.5 +/- 0.8 | |
Additional fluid should be provided when consuming a hyperosmotic medical food mixture (32) | 91 | 100 | RD If total fluid is within guidelines and no GI problems then would not add | 6.0 +/- 0.8 | |
BCAA Supplementation | |||||
If plasma ILE or VAL are below desired range, they should be supplemented by using solution/pre-weighed powders of these the L-amino acids added to a BCAA-free medical food (26) | 100 | 83 | MD may need supplement even if "normal". 2 RD also try increasing natural protein in diet | 5.9 +/- 0.8 | |
ILE and VAL may be supplemented using LEU-free medical food (e.g., I-Valex) in combination with BCAA-free medical food (27) | 46 | 50 | 2 MDs and 3 RDs lack of flexibility, can't titrate ILE and VAL separately | 4.4 +/- 1.4 Low agreement | |
Energy Recommendation | |||||
Meeting the age-appropriate DRI for energy should be sufficient for individuals with classical MSUD (28) | 82 | 100 | 5 RDs adjust based on weight, growth, metabolic control and protein-sparing | 5.5 +/- 1.0 | |
When to Consume | |||||
Medical food should be prescribed to consume at least 3 times/day (29) | 100 | 100 | 6.2 +/- 0.6 | ||
Medical food without BCAA and intact protein with BCAA should be prescribed to be consumed together to enhance anabolism (30) | 73 | 83 | RD some patients find this difficult because full after medical food | 5.8 +/- 1.1 | |
Vitamin/Mineral Supplements | |||||
Should be provided to well individuals if not consuming recommended amount of medical food or if medical food choice does not provide DRI for all vitamin/minerals (31) | 100 | 100 | 6.6 +/- 0.5 | ||
Timing of Blood Samples | |||||
Blood samples for plasma amino acid analysis should be taken 2 or more hr after food/medical food consumption (33) | 82 | 67 | MD get them when we can 3 RDs impractical, random captures full variation of amino acid levels | 5.5 +/- 1.4 | |
Blood samples for plasma amino acid analysis should be taken in morning before food/medical food consumption (34) | 36 (27% disagree) | 50 (33% disagree) | 6 RDs try for consistent times RD morning sample could help determine baseline AA levels | 4.2 +/- 6.8 Low agreement | |
Monitoring | |||||
Plasma transthyretin should be used as most reliable indicator of recent protein status (35) | 82 (17% disagree) | 33 (9% disagree) | RD along with AA profile MD growth as indicator | Large discrepancy between RD and MD | 4.9 +/- 1.3 Low agreement rating |
DNPH should be used for home keto acid monitoring whenever clinically appropriate (36) | 64 | 50 | MD Don't do, stuff is hazardous | Harm noted | 4.9 +/- 1.6 Low agreement |
Ketone urinalysis strips should be used for home monitoring of ketones whenever clinically appropriate (37) | 82 | 83 | 2 MDs easier than DNPH and meant for home use | Does "clinically appropriate" need to be clarified? | 5.3 +/- 1.2 |
Plasma LEU should be routinely monitored as best marker of BCAA control in MSUD (38) | 100 | 82 | MD + 5 RDs in combination with other amino acid levels MD LEU/ALA ratio probably superior RD full panel allows ratios to be calculated | 5.7 +/- 0.9 | |
Laboratory (38-44) See TABLE #10, Delphi Round 1 - Lab Test Frequency for Medically Stable Individuals | |||||
Anthropometrics | |||||
All infants and children: height, weight, and head circumference should be assessed at each clinic visit (45a) | 100 | 100 | 6.7 +/- 0.5 | ||
Adolescent: height, weight and BMI should be assessed at each visit (45b) | 100 | 100 | 6.7 +/- 0.5 | ||
Adults: weight and BMI should be assessed at each visit (45c) | 100 | 100 | 6.7 +/- 0.5 | ||
Developmental assessment / formal cognitive testing should be done on all children (46) | 100 | 100 | MD hard to get reimbursed, rely on school system 3 RD not available | Clarify general developmental assessment vs. formal cognitive testing | 6.4 +/- 0.7 |
Dietary Intake Assessment | |||||
Dietary intake data should be assessed whenever blood sample taken for analysis (47) | 82 | 100 | MD better to have samples even without diet record | 5.8 +/- 1.4 | |
Dietary intake data should be analyzed whenever blood sample taken for analysis (48) | 64 (36% disagree) | 100 | MD analyze q 3 mo RD time consuming; now easier with metabolic pro | Discrepancy between RD and MD | 5.0 +/- 1.5 |
Dietary intake data should be assessed when individual seen in clinic (49) | 100 | 100 | RD we ask for diet records | 6.3 +/- 0.6 | |
Dietary intake data should be analyzed when individual is seen in clinic (50) | 73 (18% disagree) | 100 | RD not always necessary; time constraints impossible to do in clinic-report back later | Discrepancy between RD and MD | 5.6 +/- 1.3 |
Docosohexanoeic acid (DHA) should be supplemented (56) | 82 (9% disagree) | 0 (33% disagree) | RD should be individual recommendation depending on age RD yes based on recent evidence | Large discrepancy between MD and RD | 4.4 +/- 1.1 Low agreement rating |
Plasma BCAA Management Goals | |||||
If offending amino acids are >10% below normal values, more intact protein should be added to diet (57) | 100 | 100 | Should LEU, ILE, VAL be named? | 6.0 +/- 0.6 | |
VAL and ILE may be somewhat above the normal range (with LEU in desired treatment range) to avoid possible deficiencies (58a) | 91 | 83 | 5.6 +/- 1.1 | ||
LEU concentrations up to 400 micromolar (5.2 mg/dl) with other BCAA in desired range (58b) | 27 (55% disagree) | 33 (50% disagree) | 3.8 +/- 1.1 Strong disagreement | ||
LEU concentrations up to 300 micromolar (4.0 mg/dl) with other BCAA in desired range (58c) | 36 (36% disagree) | 83 (0% disagree) | MD + 2 RD goal is 50-200 micromolar RD 200-250 2 RD depends on age and clinical presentation | Large discrepancy between MD and RD | 4.5 +/- 1.6 Low agreement rating |
NEW DIAGNOSIS | |||||
Clinical Statement (Item # on survey) | RD % Agreement n=11 | MD % Agreement n=6 | Notable Comments | Discussion Points for Consideration | Agreement Rating (1-7) Mean +/- SD |
All individuals with MSUD should be assessed for thiamine responsiveness (51) | 100 | 83 | 6.1 +/- 0.9 | ||
Appropriate dosage for testing thiamine responsiveness is 100 mg/d (52) | 73 | 83 | MD some need higher dose | 5.4 +/- 0.9 | |
The duration of trail of thiamine responsiveness should be at least one month unless clear response seen sooner (53) | 73 | 67 | MD may need longer RD need to monitor diet for major changes that could confound interpretation | 5.4 +/- 1.0 | |
Thiamine responsiveness should be evaluated only after the patient and his/her BCAA levels have been stabilized (54) | 46 (18% disagree) | 67 (17% disagree) | 3 RD not sure, don't have experience | Discrepancy between MD and RD | 4.7 +/- 1.5 Low agreement |
All newly diagnosed with MSUD should be given thiamine immediately regardless of BCAA levels or clinical stability (55) | 64 | 50 | 4.9 +/- 1.6 Low agreement |
CRITICAL ILLNESS | |||||
Clinical Statement (Item # on survey) | RD % Agreement n=11 | MD % Agreement n=6 | Notable Comments | Discussion Points for Consideration | Agreement Rating (1-7) Mean +/- SD |
If hemodialysis. peritoneal dialysis or exchange transfusion is utilized to reduce concentration of BCAA and their keto acids, it should be accompanied by aggressive nutritional support including energy, fluid and BCAA-free amino acid mixture (69) | 100 | 100 | MD should be done even if dialysis isn't required | More details needed regarding "aggressive" nutritional support See comments for (70) | 6.5 +/- 1.1 |
IV fluids with 10% dextrose should be provided at 1.5 to 2 times maintenance (70) | 91 | 83 | MD RD risk of brain edema is great, evaluate to determine if fluid restriction is needed RD monitor NA and water balance, 2 X may be too much RD may need higher % dextrose to reverse catabolism, MD RD may need lipids to meet caloric needs | Harm pointed out | 5.8 +/- 1.7 |
DIAGNOSIS OR CRITICAL ILLNESS | |||||
Comatose patients should be prescribed parenteral nutrition providing adequate BCAA-free amino acids, glucose and lipid (71) | 100 | 100 | MD need to use enteral AA mixture MD try NG tube with infants if possible MD We do not use BCAA-free solution, we use insulin and mannitol for brain edema 4 RD Use gut if possible 2 RD Provide BCAA (ILE, VAL) as soon as pt can tolerate to prevent catabolism | 6.1 +/- 0.7 | |
20% intralipids should be provided at 2 g/kg body weight per day (72) | 81 | 100 | MD RD use to maximize total calorie RD Base on Kcal needs to provide approx 50% of calories RD Depends on fluids and dextrose in PN | 5.8 +/- 1.0 | |
To allow sufficient glucose for anabolism, insulin should be required to prevent hyperglycemia (73) | 81 | 83 | MD insulin MAY be needed 2 RD individually asses, monitor blood glucose levels MD Reason is to provide anabolic hormones to maximize protein accretion. Glucose levels not <150 | 5.5 +/- 1.5 | |
Careful monitoring of hydration, electrolytes and neurological status is necessary to prevent cerebral edema (74) | 100 | 100 | MD mannitol and hypertonic saline are also required | 6.5 +/- 0.5 | |
Enteral feedings, total or partial should be introduced as soon as possible (75) | 100 | 100 | 6.5 +/- 0.5 | ||
Each of the BCAA should be introduced at concentrations that provide the lower limit of recommended intake of the amino acid for age/weight (76) | 91 | 83 | MD agree IF this is after LEU levels have been decreased with treatment 2 RD depends on blood values, titrated on individual basis MD VAL and ILE need to be provided at higher levels RD 20-120 mg/kg/d ILE, VAL | 5.5 +/- 1.2 | |
ILE and VAL supplementation should begin when plasma concentrations fall to the upper limit of the accepted treatment range (77) | 91 | 67 | MD +2 RD sooner, depending on other indicators of catabolism | 5.4 +/- 1.3 | |
LEU (from intact protein or complete amino acid mixture) should be introduced when plasma levels fall to the upper limit of the accepted treatment range (78) | 91 | 83 | MD RD sooner, individually assessed based on other indicators of catabolism RD also based on time passed without natural protein (usually begin ¼ usual goal x 24 hr, then increase by 1/4s to full goal with time(usually every 24 hr) and based on blood levels and/or DNPH | 5.5 +/- 1.1 | |
SICK DAY (AT HOME) PROTOCOLS | |||||
Clinical Statement (Item # on survey) | RD % Agreement n=11 | MD % Agreement n=6 | Notable Comments | Discussion Points for Consideration | Agreement Rating (1-7) Mean +/- SD |
Should be individualized (79a) | 100 | 100 | 6.6 +/- 0.5 | ||
Should include appropriate guidelines for monitoring keto acids and clinical status (79b) | 100 | 100 | 6.4 +/- 0.6 | ||
Should include appropriate guideline for decreasing BCAA (79c) | 100 | 100 | 6.5 +/- 0.5 | ||
Should include appropriate guidelines for maintaining fluid and energy intake (79d) | 100 | 100 | RD Should include guidelines for providing adequate calories without protein | Fluid and energy could be separate recommendations | 6.5 +/- 0.5 |
Should include emergency contact information (79e) | 100 | 100 | 6.6 +/- 0.5 |
WOMEN & PREGNANCY | |||||
Clinical Statement (# on survey) | RD % Agreement n=11 | MD % Agreement n=6 | Notable Comments | Discussion Points for Consideration | Agreement Rating (1-7) Mean +/- SD |
Note: Many respondents indicted they had no experience treating pregnant women with MSUD | 82% of RDs | 83% of MDs | |||
Birth control medication may help minimize menstrual cycle-induced BCAA fluctuations (59) | 46 | 67 | 4.8 +/- 1.2 Low agreement rating | ||
Pregnancy | |||||
Guided by frequent laboratory monitoring, BCAA and protein intake should be increased throughout pregnancy to meet increased requirements (60) | 100 | 100 | High agreement for many items could be due to the general nature of the statements | 6.4 +/- 0.5 | |
Poor nutrient intake due to pregnancy-related nausea and vomiting should be treated aggressively to avoid endogenous protein catabolism (61) | 100 | 100 | Are recommendations needed for how to do this? | 6.5 +/- 0.5 | |
Carnitine should be supplemented if plasma free carnitine is below the established normal range (64) | 82 (0% disagree) | 33 (50% disagree) | MD whose normal range? MD, RD have not seen it low in this pop. MD not issue in MSUD | Large discrepancy between MD and RD Can this issue be resolved with evidence? | 4.9 +/- 1.9 Low agreement rating |
Vitamin and mineral supplementation should be evaluated individually based on specific medical food prescribed, dietary adherence and the pregnant patient's laboratory assessment (65) | 100 | 83 | Is there any harm in giving to all (i.e., to treat like other pregnant women)? | 6.4 +/- 0.8 | |
Lab Tests (62, 63) See TABLE #10, Delphi Round 1 - Lab Test Frequency for Medically Stable Individuals | |||||
Delivery & Past Partum | |||||
Adequate energy should be provided during delivery and for 6 weeks postpartum to prevent catabolism (66) | 100 | 100 | MD will be catabolism of uterus no matter what RD at least this long | 6.2 +/- 0.8 | |
Monitoring of metabolic labs should continue at least 6 weeks post partum (67) | 100 | 83 | 6.1 +/- 0.8 | ||
After delivery, less protein (medical food and intact protein) should be prescribed than during pregnancy unless breastfeeding (68) | 91 | 67 | RD adjust based on amino acid levels | 5.5 +/- 1.3 |
LIVER TRANSPLANT | |||||
Clinical Statement (# on survey) | RD % Agreement n=11 | MD % Agreement n=6 | Notable Comments | Discussion Points for Consideration | Agreement Rating (1-7) Mean +/- SD |
Note: Many respondents indicated no experience with MSUD liver transplantation | 72%of RDs | 67% of MDs | |||
Individuals with MSUD who have had a liver transplant can safely consume a diet with unrestricted BCAA content (80) | 63 | 50 | 2 MD + 3 RD note no experience | 5.1 +/- 1.2 Moderate agreement | |
Can expect to have plasma BCAA and urinary keto acids in the normal range (81) | 63 | 50 | MD Alloisoleucine may be slightly elevated and may rise when sick but appears to have no clinical consequence | 5.1 +/- 1.2 | |
May need nutritional counseling to transition from a diet with medical food and very low protein foods to a "regular diet" with the DRI for protein and energy (82) | 91 | 83 | 6.0 +/- 1.0 | ||
Should continue to have plasma amino acids analyses whenever liver function tests are ordered (83) | 73 (18% neither agree or disagree) | 33 (50% neither agree or disagree) | MD, RD once/year RD Monthly for 6-12 months post transplant, always during serious illness (e.g., acute rejection, severe dehydration, etc.) and yearly after 12 months | Large discrepancy between MD and RD | 4.9 +/- 1.2 Low agreement rating |
Should be monitored for growth and nutritional status (84) | 100 | 83 | MD every 6 months MD, RD reasonable based on other patients who have had a liver transplant | 6.3 +/- 0.8 |
Coding and Analysis
Clinical practice statements were rated on a 7 point scale. A mean agreement rating and standard deviation for all respondents was calculated and is shown in the last column. Items with an agreement rating score of less than 5 should be discussed and may be withdrawn.
Completely disagree | Disagree | Somewhat disagree | Neither agree or disagree | Somewhat agree | Agree | Completely Agree |
1 | 2 | 3 | 4 | 5 | 6 | 7 |
Recoded as Disagree | Recoded as Agree |
For comparison between metabolic dietitians and physicians, the rating scale was collapsed to 1 to 3 = disagree, 4 = neither agree or disagree, and 5 to 7 = agree. The percents of RDs and MDs agreeing with each statement are reported in the second and third columns.
Comparison of RD and MD views:
Notable Comments summarized information written in by respondents.
Discussion Points for Consideration identifies issues to be addressed by the core team or work group, Nominal Group Meeting participants and/or in the second Delphi survey round.
Findings from Delphi Survey Round 2
Conducted July 2012
Clinical Statement (Item # on survey) | RD % Agreement n=11 | MD % Agreement n=6 | Notable Comments | Discussion Points for Consideration | Agreement Rating Mean +/- SD |
BCAA levels when well | |||||
< 5 yrs, LEU upper limit 200 (15) | 100 | 71.4 | Normal AAA levels, allow more (250, 500) | Answers ranged from agree to disagree | 5.68 |
> 5 yrs, LEU upper limit 300 (16) | 75 | 57 | Similar recommendations to < 5 years | 4.84 Low agreement rating | |
All ages, LEU lower limit 75-100 (17) | 83 | 85.7 | Most comments state normal range, which may differ from lab to lab | One MD strongly disagrees - but no comment | 5.0 |
All ages, ILE and VAL (18) | 83 | 86 | Usually higher than nl range | 6.0 | |
Acute illness | |||||
Aggressive increase anabolism, etc (19) | 100 | 100 | 6.55 | ||
LEU elimination no more than 48 hr (20) | 100 | 83 | One complete disagree- may need up to 4 days | 6.16 | |
BCAA-free protein at 120-150% of usual (21) | 83 | 66 | 150 may be excessive | 5.27 | |
Energy intake at 100-150% (22) | 83 | 100 | 150 maybe excessive | 5.77 | |
Fluid intake at 100-150% (23) | 92 | 67 | May need to restrict, Need Na<135 | Discrepancy between RD and MD | 5.5 |
Reintroduction of LEU, at to (24) | 92 | 67 | Consider LEU levels, brain edema; would add back at 100% | 5.72 | |
Re intro of LEU when plasma LEU at upper level of tx range (25) | 58 | 83 | If plasma levels are falling rapidly, may add sooner | Discrepancy between RD and MD | 5.0 |
Use of TPN if enteral not possible (26) | 100 | 83 | Because of lack of availability in first 24 hr, often must use only glucose and lipids | 6.05 | |
For TPN follow ASPEN guidelines(27) | 66.7 | 33.3 | May start TPN sooner (Aspen guidelines were not familiar to all) | Discrepancy between RD and MD | 4.27 Low agreement rating |
ILE and VAL supplementation (28) | 92 | 83 | 6.33 | ||
Mild illness | |||||
Factors to consider for managing at home (29) | 100 | 100 | 6.27 | ||
Reduce intact PRO by 50-100%, replace with BCAA-free (30) | 100 | 100 | Or more to get extra KCAL | 6.0 | |
LEU restriction for ≤ 48 hr (31) | 100 | 100 | With gradual reintroduction, some may need longer restriction | 6.44 | |
Adequate KCAL (32) | 100 | 100 | 6.55 | ||
Continue or add VAL, ILE (33) | 100 | 100 | At 10-15mg/kg | 6.16 | |
Monitor physical, clinical signs of illness (34) | 100 | 100 | 6.61 | ||
Monitor for urine a keto acids (35) | 92 | 67 | Not always available, use keto sticks for ketones | 5.38 | |
Maternal MSUD | |||||
Monitoring to ensure meeting extra needs (36) | 100 | 100 | Limited experience | 6.55 | |
Use of BCAA-free medical food (37) | 92 | 100 | 6.27 | ||
Plasma BCAA in same target range as non-pregnant (38) | 83 | 83 | MD (1) may want a little higher; RD (1) may want a little lower | 5.55 | |
Treat aggressively nausea etc (39) | 100 | 100 | 6.22 | ||
Illness guidelines same as non-pregnant (40) | 56 | 83 | More aggressive with closer monitoring | 5.0 | |
Vit and mineral supplementation per case (41) | 100 | 100 | 6.47 | ||
IV glucose and lipids during L and D (42) | 100 | 100 | 6.41 | ||
Restrict LEU post delivery (43) | 64 | 100 | Discrepancy between RD and MD | 5.4 | |
Close monitoring 6 weeks (44) | 92 | 100 | 6.11 | ||
Nutrient requirements for breastfeeding MSUD woman (45) | 73 | 66 | 5.29 | ||
Breast milk is appropriate LEU source for MSUD baby (46) | 100 | 83 | 6.17 | ||
Using expressed breast milk with BCAA-free requires close monitoring (47) | 100 | 100 | 6.05 | ||
Feeding at the breast (48) | 92 | 67 | Possible with close monitoring | Discrepancy between RD and MD | 5.58 |
Liver transplant | |||||
In metabolic control prior (49) | 82 | 83 | Optimal, but those needing this form of Tx are those having the most problem with control | 5.8 | |
Minimize catabolism perioperatively (50) | 91 | 83 | 5.9 | ||
Regular diet after transplant (51) | 82 | 100 | 5.88 | ||
Transition counseling needed(52) | 100 | 100 | Experience with pt >10 who had difficulty including wgt loss | 6.52 | |
Monitor for growth, nutritional status…(53) | 100 | 100 | SOP for transplantation | 6.64 | |
Thiamin | |||||
Responders have partial enz activity (54) | 54 | 100 | Large discrepancy between RD and MD | 5.41 | |
100 mg adequate (55) | 54 | 83 | Perhaps even less | Discrepancy between RD and MD | 5.11 |
4 weeksenough time for response (56) | 64 | 100 | Discrepancy between RD and MD | 5.4 | |
Need BCAA restriction with thiamin (57) | 64 | 67 | 5.0 | ||
Monitoring: 0-24 mos | |||||
3-4 clinic visits (58) | 100 | 83 | More in year 1 | 6.0 | |
Nutrition assessment with AAA (59) | 100 | 83 | 6.17 | ||
Anthropometrics with each visit (60) | 100 | 100 | 6.7 | ||
Transthyretin 2-3 x year (61) | 92 | 67 | Discrepancy between RD and MD | 5.23 | |
Iron indicies 1-2 x year (62) | 100 | 83 | 6.05 | ||
Vit D, EFA, etc annually (63) | 100 | 67 | Discrepancy between RD and MD | 5.88 | |
Monitoring: 2-8 years | |||||
2-3 clinic visits (64) | 100 | 83 | 6.17 | ||
Nutritional assessment with AAA (65) | 100 | 83 | 6.23 | ||
Anthropometrics at visits (66) | 100 | 100 | 6.76 | ||
Transthyretin 1-2 x year (67) | 100 | 83 | 5.52 | ||
Iron 1-2 x year (68) | 100 | 83 | 5.88 | ||
Vit D, EFA, etc annually (69) | 100 | 83 | 5.94 | ||
Dexa scan at age 6 (70) | 54.5 | 50 | Data not good for 6 yo, if vit D and growth is good, no need for DEXA | 4.76 Low agreement rating | |
Monitoring at home | |||||
Keto acids weekly up to 24 mos(71) | 73 | 33 | Concerns abt availability of DNPH for home use | Large discrepancy between RD and MD | 4.88 Low agreement rating |
Keto acids monthly in well 2-8 y (72) | 55 | 50 | Concerns abt availability of DPNH for home use. If available, use weekly. Need for monitoring depends of severity of mutation | 4.7 Low agreement rating | |
Keto sticks show ketones/catabolism (73) | 100 | 100 | 6.17 | ||
DNPH is more sensitive to a-ketoacids (74) | 82 | 67 | 5.88 | ||
AAA 1-2 x mos up to 24 mos (75) | 82 | 67 | 5.52 | ||
AAA monthly 2-8 yr old (76) | 91 | 83 | 6.23 | ||
Daily observation of signs and symptoms (77) | 100 | 83 | 6.17 | ||
Home monitoring with diet change and possible impending illness for all ages (78) | 100 | 100 | 6.4 |
Coding and Analysis
Clinical practice statements were rated on a 7 point scale. A mean agreement rating and standard deviation for all respondents was calculated and is shown in the last column. Items with an agreement rating score of less than 5 should be discussed and may be withdrawn.
Completely disagree | Disagree | Somewhat disagree | Neither agree or disagree | Somewhat agree | Agree | Completely Agree |
1 | 2 | 3 | 4 | 5 | 6 | 7 |
Recoded as Disagree | Recoded as Agree |
For comparison between metabolic dietitians and physicians, the rating scale was collapsed to 1 to 3 = disagree, 4 = neither agree or disagree, and 5 to 7 = agree. The percents of RDs and MDs agreeing with each statement are reported in the second and third columns.
Comparison of RD and MD views:
Notable Comments summarized information written in by respondents.
Key
Yellow | Test frequency range with >65% agreement | |
Green | Frequency with 50-64% agreement and with low RD/MD discrepancy | |
Blue | High overall support but RD/MD discrepancy | |
White | No consensus from MSUD Delphi Round 1 |
Lab Test Frequency for Medically Stable Individuals
Test/Frequency | Infants | Children 1-10 yr | Adults, Children >10 yr | Comments | ||||||
RD % | MD % | All % | RD % | MD % | All % | RD % | MD % | All % | ||
Complete blood count with differential (whole blood) | ||||||||||
Monthly | 18 | 12 | ||||||||
3 months | 9 | 6 | 9 | 6 | ||||||
6 months | 36 | 33 | 35 | 36 | 24 | 36 | 24 | |||
Yearly | 36 | 67 | 47 | 56 | 100 | 71 | 64 | 83 | 71 | |
Never | 0 | 0 | 0 | 0 | 0 | 0 | 17 | 6 | ||
Comprehensive metabolic panel | ||||||||||
Monthly | 36 | 24 | 9 | 6 | ||||||
3 months | 9 | 6 | 9 | 6 | ||||||
6 months | 18 | 33 | 24 | 36 | 17 | 29 | 46 | 17 | 35 | |
Yearly | 36 | 50 | 41 | 36 | 50 | 41 | 46 | 33 | 41 | |
Never | 0 | 17 | 6 | 9 | 33 | 18 | 9 | 50 | 24 | |
Amino Acids (plasma) | ||||||||||
Weekly | 27 | 17 | 24 | |||||||
Biweekly | 27 | 33 | 29 | 27 | 33 | 29 | 18 | 17 | 18 | |
Monthly | 27 | 33 | 29 | 27 | 0 | 18 | 27 | 0 | 18 | |
3 months | 0 | 0 | 0 | 9 | 33 | 18 | 9 | 0 | 6 | |
6 months | 18 | 0 | 12 | 36 | 0 | 24 | 38 | 67 | 47 | |
Yearly | 0 | 0 | 0 | 0 | 17 | 6 | 9 | 0 | 6 | |
Never | 0 | 17 | 6 | 0 | 17 | 6 | 0 | 17 | 6 | |
Carnitine, free, esterified and total (plasma) | ||||||||||
Monthly | 18 | 12 | ||||||||
3 months | 9 | 17 | 12 | 17 | 6 | |||||
6 months | 9 | 17 | 0 | 18 | 0 | 12 | 9 | 17 | 12 | |
Yearly | 0 | 0 | 12 | 27 | 17 | 24 | 27 | 17 | 24 | |
Never | 55 | 67 | 60 | 54 | 67 | 59 | 64 | 67 | 65 | |
Transthyretin (plasma) | ||||||||||
Biweekly | 9 | 6 | ||||||||
Monthly | 9 | 6 | 9 | 6 | 9 | 6 | ||||
3 months | 18 | 12 | 0 | 0 | 0 | |||||
6 months | 27 | 33 | 29 | 36 | 17 | 29 | 27 | 17 | 24 | |
Yearly | 36 | 50 | 41 | 45 | 33 | 41 | 46 | 17 | 35 | |
Never | 0 | 17 | 6 | 9 | 50 | 24 | 18 | 67 | 35 | |
Ferritin (plasma) | ||||||||||
Monthly | 9 | 6 | ||||||||
3 months | 18 | 12 | 0 | |||||||
6 months | 36 | 17 | 24 | 36 | 29 | 9 | 6 | |||
Yearly | 27 | 67 | 47 | 45 | 50 | 41 | 73 | 50 | 65 | |
Never | 18 | 17 | 18 | 18 | 59 | 24 | 18 | 50 | 29 | |
Test/Frequency | Infants | Children 1-10 yr | Adults, Children >10 yr | Comments | ||||||
RD % | MD % | All % | RD % | MD % | All % | RD % | MD % | All % | ||
Essential fatty acid profile (plasma) | Write in: | |||||||||
6 months | ||||||||||
Yearly | 27 | 33 | 29 | 73 | 33 | 59 | 55 | 33 | 47 | |
Never | 73 | 67 | 71 | 27 | 67 | 41 | 46 | 67 | 53 | |
Essential fatty acid profile (erythrocyte) | Write in: | |||||||||
6 months | 9 | 6 | ||||||||
Yearly | 46 | 17 | 35 | 64 | 17 | 47 | 46 | 17 | 35 | |
Never | 46 | 83 | 59 | 36 | 83 | 53 | 54 | 83 | 65 | |
Folate (erythrocyte) | ||||||||||
6 months | 9 | 6 | 9 | 6 | ||||||
Yearly | 55 | 17 | 41 | 64 | 17 | 47 | 73 | 17 | 53 | |
Never | 36 | 83 | 53 | 27 | 83 | 47 | 27 | 83 | 47 | |
Vitamin B12 (serum) | ||||||||||
6 months | 18 | 12 | 9 | 6 | ||||||
Yearly | 36 | 50 | 41 | 73 | 50 | 65 | 82 | 50 | 71 | |
Never | 46 | 50 | 47 | 18 | 50 | 28 | 18 | 50 | 29 | |
Vitamin D 25-OH (plasma) | ||||||||||
3 months | 9 | 6 | ||||||||
6 months | 9 | 17 | 12 | 46 | 29 | 18 | 12 | |||
Yearly | 64 | 67 | 65 | 46 | 100 | 65 | 73 | 83 | 76 | |
Never | 18 | 17 | 18 | 9 | 0 | 6 | 9 | 17 | 12 | |
Trace minerals (selenium, zinc) (serum) | ||||||||||
3 months | 9 | 6 | ||||||||
6 months | 18 | 12 | 9 | 6 | ||||||
Yearly | 36 | 17 | 29 | 82 | 16 | 59 | 82 | 17 | 59 | |
Never | 36 | 83 | 53 | 9 | 83 | 35 | 18 | 83 | 41 | |
Amylase (serum) | Amylase write in: | |||||||||
3 months | 17 | 6 | ||||||||
6 months | 9 | 0 | 6 | |||||||
Yearly | 18 | 0 | 12 | 18 | 17 | 18 | 9 | 17 | 12 | |
Never | 73 | 83 | 77 | 82 | 83 | 82 | 91 | 83 | 88 | |
Lipase (serum) | Lipase write in: | |||||||||
3 months | 17 | 6 | ||||||||
6 months | 18 | 0 | 12 | 9 | 6 | |||||
Yearly | 9 | 0 | 6 | 18 | 17 | 18 | 27 | 17 | 24 | |
Never | 73 | 83 | 77 | 73 | 83 | 77 | 73 | 83 | 77 | |
Lipid profile (total chol, HDL, LDL, triglycerides) (serum) | Lipid profile write in: | |||||||||
3 months | ||||||||||
6 months | 9 | 6 | ||||||||
Yearly | 36 | 17 | 29 | 46 | 33 | 41 | 73 | 17 | 53 | |
Never | 55 | 83 | 65 | 55 | 66 | 59 | 27 | 83 | 47 | |
Organic acids (urine) | ||||||||||
Monthly | 18 | 0 | 12 | 18 | 12 | |||||
3 months | 9 | 17 | 12 | 0 | 0 | |||||
6 months | 9 | 17 | 12 | 9 | 17 | 12 | 8 | 6 | ||
Yearly | 27 | 0 | 18 | 27 | 17 | 24 | 36 | 33 | 35 | |
Never | 36 | 67 | 47 | 46 | 67 | 53 | 55 | 67 | 59 | |
DEXA scan beginning at age 6 | Write in: | |||||||||
Yearly | NA | NA | NA | 64 | 67 | 65 | 91 | 33 | 71 | |
Never | 36 | 33 | 35 | 9 | 67 | 29 |
Assumptions:
Comment from Delphi participant:
Summary of Findings
Do not do: | No consensus: | |
Amylase | Folate | |
Lipase | Trace minerals | |
Carnitine | Lipid profile in children and adults | |
Essential fatty acid | Amino acids (need to separate out BCAA | |
Organic acid (urine) |
Test | Infants | Children | Adults & Children >10 yr |
CBC | 6 mo or yearly | Yearly | Yearly |
Comprehensive Metabolic Panel | 6 mo or yearly | 6 mo or yearly | 6 mo or yearly |
Transthyretin | 6 mo or yearly | 6 mo or yearly | 6 mo or yearly |
Ferritin | 6 mo or yearly | 6 mo or yearly | Yearly |
Vitamin B12 | ? | Yearly | Yearly |
Vitamin D 25 OH | Yearly | Yearly | Yearly |
DEXA | NA | Yearly | Yearly |
Note: this table accompanies TABLE #8, Findings from Delphi Survey Round 1.
Classification1 | Complete | No added fat | Amino Acids |
Nutrient Profile | Amino acids, carbohydrates, fats, vitamins and minerals | Amino acids, carbohydrates, vitamins and minerals | No carbohydrates or fats; few or no vitamins and minerals |
Pro: energy ratio (PRO g/100kcal)2 | Low to medium | Medium to high | High |
Forms | Powder, bars | Powder, ready-to-drink | Powder |
Products designed for infants | BCAD 17, Ketonex-16, MSUD Analoge | None | None |
Products designed for children3 | BCAD 27 Complex Junior MSD5 Complex Essential MSD5 Complex MSD Amino Acid Bars10 Ketonex-26 | Camino Pro MSUD9 Milupa MSUD 25 MSUD Gel8 MSUD Express 158, MSUD Express 208 MSUD Cooler 158 MSUD Lophlex LQ5 MSUD Maxamaid5 | None |
Products designed for adolescents and adults4 | BCAD 27 Complex Essential MSD5 Complex MSD Amino Acid Bars10 Ketonex-26 | Camino Pro MSUD9 Milupa MSUD 25 MSUD Express 158 MSUD Express 208 MSUD Cooler 158 MSUD Lophlex LQ5 MSUD Maxamum5 | Complex MSD Amino Acid Blend5a |
1. Examples of products available in the U.S. as of August 2014. Inclusion in table does not represent endorsement
2. Energy/Protein ratio categories ((PRO g/100kcal): High: 11-25; Medium 5-10; Low <5
3. Some products not appropriate for children <4 years; check manufacturer’s information for nutrient profile
4. Some products may be used before adolescence, especially if used in combination with other products, depending on clinical circumstances
5. Nutricia North America, Gaithersburg, MD (including Applied Nutrition)
6. Abbott Nutrition, Columbus OH
7. Mead Johnson Nutrition, Evansville IN
8. Vitaflo USA, Alexandria, VA
9 Cambrooke Foods, Ayer, MA
10. Complex MSD Amino Acid Bars have a low PRO: energy ratio but no added vitamins and minerals.
AGE | LEU mg/kg BW | ILE mg/kg | VAL mg/kg | PRO gm/kg | ENERGY kcal/kg |
4-8 years | 35-65 | 20-30 | 30-50 | 1.3-2.0 | 50-120 |
As there is a range in the recommendations for the BCAA, energy and PRO, monitoring growth, clinical status and biochemical markers is essential when prescribing the nutrient intake for any individual with MSUD. There may be some individuals who will need intakes outside the recommended ranges for optimal outcome. If monitoring results are consistent with good control, dietary modifications such as introduction of solid foods or change in formula mixture should be based on current intake.
Meal | Food/beverage items | Amount | LEU mg | PRO g | Energy kcal |
Breakfast | Cereal, puffed rice | 1 cup (14 g) | 74 | 0.9 | 56 |
Banana | 1 medium | 80 | 1.3 | 105 | |
Rice milk | 4 oz | 9 | 0.2 | 24 | |
BCAD-2 | 31 g, made up to a total of volume of 8 oz with water | 0 | 7.4 | 127 | |
Lunch | Half sandwich: low-protein bread apple butter | 1 slice 2 TBS | 7 7 | 0.1 0.1 | 130 59 |
Carrot sticks | 36 g | 37 | 0.3 | 15 | |
Wise onion rings | 1 pkg (14 g) | 7 | 0.3 | 70 | |
Lemon pudding cup | 1 snack cup | 9 | 0.1 | 124 | |
MSUD cooler™ 15 | 1 pouch (130 mL) | 0 | 15 | 92 | |
Snack | Popcorn, buttered | 1 cup | 84 | 0.7 | 43 |
Apple juice | 4 oz | 3 | 0.1 | 53 | |
Dinner | Pasta, low-protein, cooked | 1/3 cup, dry | 16 | 0.3 | 203 |
Tomato sauce | ½ cup | 47 | 1.6 | 29 | |
Broccoli, cooked | ½ cup | 115 | 1.9 | 27 | |
Low-protein bread, toasted with garlic butter | 1 slice 1 tsp | 7 4 | 0.1 0 | 130 34 | |
Watermelon, diced | 1 cup | 27 | 0.9 | 46 | |
BCAD-2 | 31 g made up to a total volume of 8 oz with water | 0 | 7.4 | 127 | |
TOTALS | 533 | 38.7 | 1494 | ||
Per kg IBW (18 kg) | 30 mg | 2.2 g | 83 kcal | ||
Per kg actual weight (20 kg) | 27 mg | 1.9 g | 75 kcal |
AGE | LEU mg/kg | ILE mg/kg | VAL mg/kg | PRO g/kg | ENERGY kcal/kg | FLUID mL/kg |
0 to 6 mos | 40-100 | 30-90 | 40-95 | 2.5-3.5 | 95-145 | 125-160 |
As there is a range in the recommendations for the BCAA, energy and PRO, monitoring growth, clinical status and biochemical markers is essential when prescribing the nutrient intake for any individual with MSUD. Some individuals may need intakes outside the recommended ranges for optimal outcome.
This table is an excerpt of TABLE #4, Recommended Daily Nutrient Intakes of BCAA, PRO, ENERGY and Fluids for Infants, Children and Adults with MSUD (when well) from the Nutrition Management Guideline for MSUD
Components | Amount | LEU mg | ILE mg | VAL mg | PRO gm | Energy Kcal |
Breast milk (mature) | 100 mL | 100 | 58 | 56 | 1.07 | 72 |
MSUD Analog™ (Nutricia) | 100 g | - | - | - | 13 | 475 |
Similac Advance™ | 100 g | 1080 | 575 | 640 | 10.6 | 510 |
This table is an excerpt of TABLE #11, Classification of Medical Foods for MSUD from the Nutrition Management Guideline for MSUD
Components | AMT | LEU mg | ILE mg | VAL mg | PRO gm | ENERGY Kcal |
Breast milk | 266 mL | 266 | 154 | 149 | 2.85 | 192 |
MSUD Analog™ | 52 g | - | - | - | 6.76 | 248 |
Non-PRO energy source | 0 | 0 | 0 | 0 | 0 | 0 |
Supplemental VAL | 10.6 mL1 | - | - | 106 | - | - |
Supplemental ILE | 7.4 mL1 | - | 74 | - | - | - |
Final volume | 600 mL | |||||
TOTAL | 600 mL/ 20 fl oz | 266 | 228 | 255 mg | 9.6 g | 440 kcal 22 kcal/oz |
Per kg | 70 mg | 60 mg | 67 mg | 2.5 g | 116 kcal |
1 Derived from 1% solutions containing 10 mg/mL. Alternatively, powders containing 106 mg pure VAL or 74 mg pure ILE can be added during preparation of the formula mix.
Components | Amount | LEU mg | ILE mg | VAL mg | PRO g | Energy Kcal |
Breast milk | 270 mL | 270 | 157 | 141 | 2.89 | 194 |
MSUD Analog™ | 55 g | - | - | - | 7.15 | 261 |
Non-PRO energy source | 0 | 0 | 0 | 0 | 0 | 0 |
Supplemental VAL | 10 mL | - | - | 100 mg | - | - |
Supplemental ILE | 7 mL | - | 70 | - | - | - |
Final volume | 600 mL | |||||
TOTAL | 600 mL/ 20 fl oz | 270 mg | 227 mg | 241 mg | 10.0 g | 455 kcal 23kcal/oz |
Approximate/kg BW | 158 mL | 71 mg | 60 mg | 63 mg | 2.6 g | 120 kcal |
Components | Amount1 | LEU mg | ILE mg | VAL mg | PRO g | Energy Kcal |
Similac Advance™ | 25 g | 266 | 144 | 160 | 2.7 | 128 |
MSUD Analog™ | 55 g1 | - | - | - | 7.3 | 266 |
Non-PRO energy source (ProPhree™)2 | 10 g | - | - | - | - | 48 |
Supplemental VAL | 8 mL 1,3 | - | 80 | - | - | - |
Supplemental ILE | 10 mL 1,3 | - | - | 100 | - | - |
Final volume | 600 mL | |||||
TOTAL | 600 mL (20 fl oz) | 266 | 224 | 260 | 10.0 | 442 kcal 22 Kcal/ oz |
Per kg BW | 158 mL | 70 mg | 60 mg | 67mg | 2.6 g | 116 kcal |
1 It will not adversely affect outcome to round amounts: e.g,.55 g Analog; 8 mL supplemental VAL; 10 mL supplemental ILE
2 Alternately, the formula mixture can be prepared using 65 g MSUD Analog™, with the additional 10 g of the BCAA-free medical food providing the 48 kcal.
3 1% solutions containing 10 mg/mL. Alternatively, powders containing 80 mg pure VAL or 100 mg pure ILE can be added to the formula mixture
AGE | LEU mg/kg | ILE mg/kg | VAL mg/kg | PRO g/kg | ENERGY kcal/kg | FLUID mL/kg |
6 to 12 mo | 40-75 | 30-70 | 30-80 | 2.5-3.0 | 80-135 | 125-145 |
As there is a range in the recommendations for the BCAA, energy and PRO, monitoring growth, clinical status and biochemical markers is essential when prescribing the nutrient intake for any individual with MSUD. Some individuals may need intakes outside the recommended ranges for optimal outcome. If monitoring results are consistent with good control, dietary modifications such as introduction of solid foods or change in formula mixture should be based on current intake.
Components | Amount | LEU mg | ILE mg | VAL mg | PRO g | Energy kcal |
Good Start™ | 33 g | 378 | 190 | 196 | 3.7 | 169 |
Ketonex-1 ™ | 105 g | 0 | 0 | 0 | 15.8 | 504 |
Isoleucine50™ | 2 sachets | ~ | 100 | ~ | 0.1 | 31 |
Valine50™ | 2 sachets | ~ | ~ | 100 | 0.1 | 31 |
Water to make 32 oz final volume | ||||||
Total | 32 oz/ 960mL | 378 | 290 | 296 | 19.7 | 735 23kcal/oz |
Per kg BW | 47 mg | 36 mg | 37 mg | 2.5g | 92 kcal |
Components | Amount | LEU mg | ILE mg | VAL mg | PRO gm | Energy kcal |
Good Start™ | 30 g | 344 | 173 | 179 | 3.4 | 154 |
Ketonex-1™ | 105 g | 0 | 0 | 0 | 15.8 | 504 |
Solid foods, intact PRO | Varies | 30 | varies | Varies | ~0.5 | Varies |
Isoleucine 50 | 2 sachets | 0 | 100 | 0 | 0.1 | 31 |
Valine 50 | 2 sachets | 0 | 0 | 100 | 0.1 | 31 |
Total | 375 | 291 | 305 | 20.0 | 720 + food | |
Per kg | 47 mg | 36 mg | 38 mg | 2.5 g | ~95 kcal |
Suggested Time | Formula or Food | Amount | LEU mg | PRO gm | Energy kcal |
6 AM | Formula | 8 oz | 86 | 4.8 | 180 |
9 AM | Baby food, rice cereal, dry (mixed with water or formula from daily allotment) | 1.5 TBS | 21 | 0.3 | 15 |
Applesauce | 1 TBS | 2 | 0 | 9 | |
11 AM | Formula | 8 oz | 86 | 4.8 | 180 |
3 PM | Formula | 8 oz | 86 | 4.8 | 180 |
6 PM | Pureed sweet potatoes Applesauce | 1 TBS 1 TBS | 8 2 | 0.2 0 | 10 9 |
8 PM | Formula | 8 oz | 86 | 4.8 | 180 |
TOTAL INTAKE | 377 mg | 19.7 g | 763 kcal | ||
Per kg BW | 47 mg | 2.5 g | 95 kcal |
Component | Goal | Source(s) |
Energy | 150% of recommended 1,2 | Enteral: BCAA-free medical food and, as needed, other BCAA/PRO free energy sources - e.g., Solcarb™ (Solace Nutrition), S.O.S.™ (Vitaflo USA),Pro-Phree™ (Abbott Nutrition), Duocal™ (Nutricia); PFD™ (Mead Johnson) |
Parenteral2: 10% glucose/dextrose3, 20% Intralipids @ 2 gm/kg/day. | ||
BCAA-free AA | 120-150% of recommended | Enteral: BCAA-free medical food4 |
Parenteral: BCAA-free specialty TPN6 | ||
Fluids and electrolytes | Individualized 3,5 | Enteral: additional protein-free oral fluids,e.g., juices, sport drinks |
Parenteral5: Glucose/dextrose solutions and TPN | ||
BCAA (ILE and VAL) | 20-120 mg/kg/day6 for each | Enteral: may be added to the medical food, as weighed powder, or in appropriate volume of 1% solutions |
Parenteral: from specialty pharmacies. Or, if no parenteral form is available, use small volumes given orally, or slow drip by NG or g-tube. | ||
Insulin7 | to prevent or reverse hyperglycemia |
1. To promote anabolism, an increase in the recommended intake TABLE #4, Recommended Daily Nutrient Intakes of BCAA, PRO, ENERGY and Fluids for Infants, Children and Adults with MSUD (when well) based on age and ideal weight for healthy individuals with MSUD).
2. More concentrated solutions are possible if access is through a PICC/central line
3. Glucose solution given at a rate of 1.5-2 X maintenance is possible but never use maximum rate unless constant monitoring confirms there is no brain edema or electrolyte imbalance
4. Provide not only the recommended PRO for age and size, but also replace the sources of intact PRO removed to restrict BCAA and add additional energy
5. Although dehydration and acid-base imbalance are often seen during illness, very careful monitoring is needed to prevent cerebral edema from fluid overload and electrolyte imbalance
6. To reach and maintain blood VAL and ILE goals of ~ 400 µM, added VAL and LEU are needed during the acute phase of illness to help decrease LEU levels by providing substrate for PRO synthesis and prevent ILE and VAL deficiencies.
7. Insulin may be necessary to maximize glucose utilization and prevent hyperglycemia
Assessment | Intervals1 |
BCAA by plasma amino acids | 12 hr or as indicated |
Sodium, potassium, water balance | 12 hr or as indicated |
Glucose | 12 hr or as indicated |
Clinical signs of intracranial pressure | continuously |
Weight and urine output | Daily, or as indicated |
Urine osmolarity | Daily, or as indicated |
1. Intervals dependent on clinical judgement of intensive care and metabolic physicians as well as facility resources. For further discussion and details of acute illness care see: R.3 and R.25