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Guidelines for the Nutritional Management of Maple Syrup Urine Disease
A Practical Guide for the Use off
Nutricia's MSUD Products
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Contents
Introduction and Background
Basic Overview..................................................................04
Diet Principles....................................................................07
Diet Prescription................................................................08
Managing the Diet..............................................................10
Choice of Medical Food.....................................................11
Monitoring.........................................................................13
Illness, Surgery or Injury......................................................14
Case Studies
Case Study 1.....................................................................16
Case Study 2.....................................................................18
Case Study 3.....................................................................20
Appendix
Product Information Table...................................................22
03
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Introduction and Background
Basic Overview
Maple syrup urine disease (MSUD) is
the common name of the autosomal
recessive disorder branched-chain α-
Figure 11
Biochemistry: Metabolism of branched-chain amino acids
ketoacid dehydrogenase (BCKD)
Valine
deficiency. The branched-chain
amino acids (BCAA): leucine (LEU);
isoleucine (ILE) and valine (VAL),
Isoleucine
Aminotransferase
2-Oxoisovalerate
Leucine
Aminotransferase
2-OHisovalerate
BCKDH
2-Oxo3-methylvalerate
Alloisoleucine
BCKDH
Aminotransferase
2-Oxoisocaproate
2-Oxoisocaproate
2-OH-isocaproate
BCKDH
whether from exogenous (dietary) or
Isobutyryl-CoA
endogenous (body protein) sources,
2-Methylbutyryl-CoA
IBD
Isovaleryl-CoA
MBD
3-OH-isovalerate
Isovalerylglycine
IVD
are first deaminated and the resulting
branched-chain α-ketoacids (BCKA)
are further catabolized by BCKD as
Methylacrylyl-CoA
Tiglyl-CoA
Hydratase
Hydratase
seen in Fig 1.
Deacylase
3-OH-isovalerate
3-Methylcrotonylglycine
3-Methylcrotonyl-CoA
MCC
3-Methylglutarate
3-Methylglutaconyl-CoA
2-Methyl3-OH-butyryl-CoA
3-OH-isobutyryl-CoA
In MSUD there is an accumulation of
Tiglyl-glycine
MHBD
Hydratase
both the BCAA and BCKA. Another
BCAA, allo-isoleucine (allo-ILE),
normally not detectable, is a
distinctive marker in MSUD. A by-
DH
Methylmalonate
semialdehyde
product of accumulated ILE has a
3-OH-propionate
Methylcitrate
3-OH-3-methylglutaryl-CoA
3-Oxothiolase
HMG-CoA lyase
DH
Propionyl-CoA
distinctive odor similar to maple
syrup or burnt sugar that can be
2-Methylacetoacetyl-CoA
3.OH-isobutyrate
Acetyl-CoA
Acetoacetate
Carboxylase (PCC)
Methylmalonyl-CoA
detected in cerumen (as early as
12-24 hours after birth in an
untreated newborn with MSUD) and
in urine (by 48-72 hours).
Mutase (MCM)
Succinyl-CoA
Krebs
cycle
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
The enzyme, BCKD, is a complex of four protein subunits: E1α, E1β, E2 and E3; and disease-causing mutations have
been identified in each of these. The resulting phenotypes have been divided into 5 subtypes of MSUD2,3, as seen in Table 1
(overleaf).
The classical form of MSUD is the most common and results from mutations in the E1 subunits that cause the BCKD to
have less than 3% normal enzyme activity. Without the ability to breakdown the BCAA and the accumulation of
intermediates, the clinical signs and symptoms may appear within hours of birth.
• Elevated plasma concentrations BCAA, as well as a generalized disturbance of plasma amino acid concentration
ratios are present by 12-24 hours of age.
• Elevated branched chain α-ketoacids (BCKA) and generalized ketonuria, irritability, and poor feeding by 24-72 hours.
• Deepening encephalopathy manifesting as lethargy, intermittent apnea, opisthotonus ( a spasm of extreme
hyperextension), and stereotypical movements such as "fencing" and "bicycling" by 4-5 days.
• Coma and central respiratory failure that may occur by 7-10 days.
Other phenotypes with various degrees of partial enzyme activity include the intermediate, thiamin-responsive, and
intermittent forms of MSUD that can experience severe metabolic intoxication and encephalopathy during periods of
serious catabolic stress. The fifth type, resulting from mutations in the E3 subunit is a complex disorder that affects not
only the activity of BCKD but also α-ketoglutarate and pyruvate dehydrogenase.
1. Zschocke J et al. Vademecum Metabolicum. 3rd ed. Friedrichsdorf, Germany: Milupa GmbH & Co. KG/Schattauer; 2011:60
2. Strauss KA, et al. Maple Syrup Urine Disease in GeneReviewsTM (internet), updated 2009 at http://www.ncbi.nlm.nih.gov/books/NBK1319
3. Nutrition Management Guidelines for Maple Syrup Urine Disease (2013), a collaborative project between Southeastern Region Collaborative
(SERC) and Genetic Metabolic Dietitians International (GMDI) see at: www.GMDI.org
05
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Table 1: MSUD Phenotypes2,3
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)
Similar to intermediate. Often due to
responsive 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
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Diet Principles3
The BCAA are essential amino acids and must be consumed in the diet as substrates for protein synthesis. Human skeletal
muscle is composed of approximately 40% BCAA residues. At times when energy needs exceed energy input, endogenous
protein can be broken down and the BCAA become a viable energy source. In MSUD, the ability to use the BCAA as an
energy source is inhibited and the BCAA and BCKA accumulate to toxic levels. The BCAA competitively inhibit transport of
other large neutral amino acids, and the BCKA affect acid-base balance and neurotransmitter synthesis.
The goals of dietary intervention in MSUD are:3
• Rapidly reduce toxic metabolites by restricting dietary BCAA to amounts allowing patients to achieve and maintain
appropriate plasma BCAA amino acid concentrations for growth and health maintenance. The goals for plasma
BCAA levels are:3
LEU
VAL and ILE
50 -200 µM for those ≤5 years of age
within or slightly above the normal range for individuals
of the same age without MSUD
50 -300 µM for those >5 years of age
• Reduce catabolism
• Promote anabolism
• Monitor nutritional status and alter intake to promote normal growth, development and health maintenance
• Evaluate thiamin responsiveness if patient has residual BCKD activity; supplement if responsive
07
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Diet Prescription3
The dietary prescription for individuals with MSUD must be tailored for each patient. It is dependent on such factors as:
the amount of residual BCKD activity; age and size; and clinical and nutritional status. Diet calculations for a newly
diagnosed infant begin with the recommended intakes (Table 2) of BCAA, protein (PRO), calories (KCAL) and fluids for
individuals with MSUD. However, establishing the prescription can be done in the same stepwise manner for all individuals
with MSUD.
Step 1: Meet the LEU requirement through the use of measured quantities of intact protein from breast milk,
regular infant formula, or complete amino acid mixtures (all with known BCAA content per g PRO). Beyond infancy,
the LEU requirement is met by foods of known LEU content. Although there are age- and size- specific
recommended LEU intakes, the fine tuning of the requirement for a given patient is dictated by plasma LEU levels.
Step 2: Calculate the ILE and VAL content of the intact PRO, and add additional ILE and VAL, if needed, to meet
the requirement and to adjust plasma BCAA levels. Typically, these supplemental BCAA are prepared as 1%
solutions and added to the medical food preparation in 1 mL increments.
Step 3: Complete the protein (PRO) requirement by adding the medical food (metabolic formula) that provides a
BCAA-free mixture of amino acids (as well as other nutrients).
Step 4: Complete the energy requirement by adding non-protein calorie sources as needed. Energy needs should
be based on ideal body weight whenever possible.
Step 5: Adjust fluid volume and calculate the vitamin, mineral and micronutrient content of the final mixture; adjust
or supplement as needed.
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Table 2: Recommended Daily Intakes for Individuals with MSUD3,4
AGE
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
4. Marriage B. Nutrition Management of Patients with Inherited Disorders of Branched-Chain Amino Acid Metabolism. In: Acosta PB, ed. Nutrition
Management of Patients with Inherited Metabolic Disorders. Sudbury, MA: Jones and Bartlett Publishers; 2010:175-236
09
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Managing The Diet3
• Day-to-day diet management by the individual or his/her caregiver nearly always requires the use of a BCAA-free
medical food. Only those with the mildest forms of MSUD can meet their PRO requirement and avoid excessive BCAA
intake without using medical food. During catabolic illness, even these individuals may need to consume medical food.
• Weighing powdered medical foods (and, for infants, regular infant formula as the intact PRO/BCAA source) gives the
most accurate and consistent product. Calculations for the amount of intact PRO needed are based on LEU
requirements, and are modified by monitoring blood/plasma LEU levels. If additional ILE and/or VAL are required, these
should be added at this point. Depending on the individual’s age, water should be added to provide a final volume with
a caloric density of 20 to 30 Kcal/fluid ounce. Preparing a 24 hour supply saves time and avoids errors when measuring
small quantities. Prepared medical food mixtures should be refrigerated and used within 24 hours. For infants, only an
amount anticipated to be finished in one feeding should be placed in a nursing bottle to avoid wastage. The medical
food mixture should be consumed throughout the day. Infants should take this mixture at every feeding.
• Breast milk, with a mean LEU concentration of 1 mg/mL, is an option as the source of intact protein in infants with
MSUD.2 If expressed breast milk is used, this can be added in the appropriate volume to provide the daily required LEU.
Some infants with MSUD have been successfully managed by alternating breast feedings with bottle feedings. This
requires very careful and frequent monitoring (including plasma BCAA levels and growth) of the infant. Additional
support should be given to the lactating mother to ensure that she is consuming adequate and appropriate food and
fluids to maintain milk production.
• LEU sources for older children and adults come from the intact PRO in foods. Typically, fruits and vegetables are the
mainstay of the diet as the PRO: KCAL ratio is low, hence a larger volume of food will not have excessive LEU or other
BCAA. Even these low PRO foods must be measured and the amount of PRO or LEU calculated to meet, but not
exceed, the LEU requirement.
• Modified low PRO foods are another form of medical foods that add KCAL, variety and some normalcy to the diet. The
majority of these foods are baked goods and pastas that are prepared from the starch portion of grains rather than the
higher PRO flours.
• PRO and LEU composition for appropriate foods and medical foods can be found in resources for both patients5.6
and professionals (see references 5-9 page opposite).
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Choice Of Medical Foods
For nearly all individuals with MSUD, BCAA-free medical foods are the cornerstone of the dietary treatment throughout
their entire lives. New medical foods for MSUD have been developed over the years to respond to: the differing nutrient
requirements of each life stage, and the challenge of patient compliance by offering choices of taste and consistency.
For these reasons, Nutricia offers a wide range of products for the individual with MSUD (see Table 3 overleaf). While
each product targets a specific patient population, there can be some flexibility and overlap to achieve optimal
compliance, or improve access when cost is a limiting factor. In all cases, frequent clinical and biochemical monitoring
(see Monitoring - pg 13) is essential.
5. PKU Food List by Virginia Schuett (2010); www.pkunews.org
6. MSUD Foodlist" available at http://genetics.emory.edu/docs/Nutrition%20Docs/MSUDorderform9-29-05.pdf
7. Bowes and Church’s Food Values of Portions Commonly Used. 19th ed.
8. MetabolicPro diet analysis program at www.GMDI.org
9. USDA food composition tables at http://ndb.nal.usda.gov.
11
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Table 3: Nutricia Medical Food Characteristics
MSUD
Analog®
(per 100 g)
MSUD
Maxamaid®a
(per 100 g)
MSUD
Maxamum®a
(per 100 g)
MSUD
Lophlex LQ®a
(per 125 mL)
Form
powder
powder
powder
ready-to-drink
Availability
400 g (14.1 oz)
can
454 g (1lb) can
454 g (1lb) can
125 mL (4.2 fl oz)
pouches
Recommended
age
0-12 months
Toddlers
and young children
Older children, and
adults including
pregnant women
≥ 4 years
Added
vitamin/mineralb
yes
yes
yesd
yes
PRO equiv
13 g
25 g
40 g
20 gc
CHO
59 g total
12 g simple
47 g complex
56 g total
43 g simple
13 g complex
34 g total
28 g simple
6 g complex
9.3 g total
Simple sugars and
sweeteners
Fat
20.9 g
< 0.1 g
-
0.44 g
Fiber
-
-
-
0.5 g
DHA
-
-
-
150 mg
KCAL
475
324
305
120
KCAL: PRO
36.5
13
7.6
6
a. MSUD Lophlex LQ is flavored with real fruit juice (from concentrate), MSUD Maxamaid and Maxamum have artificial orange flavoring.
b. Vitamin and mineral content appropriate for the recommended age
c. Small amounts (< 1.5 mg/100 mL ) of BCAA from added fruit juices
d. Appropriate levels for pregnancy if additional folate is given
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Monitoring2,3
Monitoring is an essential part of MSUD management as frequent adjustments to the diet are necessary to meet nutritional,
growth and health maintenance needs while keeping the individual in metabolic control. Important markers for the MSUD
monitoring plan are:
• Signs and symptoms of catabolic illness: detection of the maple syrup, or burnt sugar, odor in the cerumen and urine
occurs when the BCAA accumulate during catabolism. Nausea and vomiting are common. Neurological signs may
include cognitive decline, hallucinations, mood swings, choreoathetosis and ataxia.
• Growth parameters: head circumference, weight for height and body mass index (BMI) for those over age 2. Care should
be taken when interpreting weight for height and BMI as those with both poor linear growth and weight gain may have
normal indices. Growth charts can be found at: www.cdc.gov/growthcharts
• Urinary ketones, ketoacids: ketones are a sign of catabolism, and α-ketoacids accumulate in the urine when the BCAA
are elevated.
• Plasma amino acids: analysis of plasma amino acids are necessary to monitor the BCAA and help assess the adequacy
of the protein intake
• Protein status: in addition to plasma amino acids, albumin, prealbumin (transthyretin) and total protein are markers to
follow to assess protein status. When these indicators suggest a need to increase PRO intake, and BCAA are in the
treatment range, PRO from medical food can be increased in 10% increments. If the LEU levels are also low, then more
intact PRO can be added.
• Nutrition status: diet intake analysis for macro- and micronutrients is recommended. When these analyses suggest
suboptimal intake, or there are clinical signs of deficiencies, further biochemical analysis for nutrients is warranted.
13
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Illness, Surgery Or Injury2,3
Any illness, injury or surgical procedure is a potential catabolic event that can result in breakdown of body protein stores,
release of BCAA and development of ketoacidosis. These events need to be taken seriously as metabolic
decompensation can develop quickly and can be life-threatening. The entire metabolic team needs to work with families
and individuals to plan for these events.
• Initiating the diet in a newly diagnosed infant: if the infant is symptomatic at the time of diagnosis, the coordinated
efforts of the intensive care team may be needed to facilitate the rapid removal of excessive BCAA and α-ketoacids,
reversal of catabolism, and the use of parenteral nutrition to provide non-BCAA, lipids, glucose, fluids and possibly
insulin. Frequent monitoring of both biochemical markers and clinical symptoms is necessary. As soon as possible,
small volumes of enteral feeds (medical food) should be introduced. When the levels of ILE and VAL fall to the upper
limit of the accepted treatment range, they should be added to facilitate anabolism of LEU (through PRO synthesis).
Although hemodialysis may be necessary when BCAA levels are extremely high, it should be accompanied by
aggressive nutritional intervention.
• Emergency protocol: every patient with MSUD should be provided with a written emergency protocol/letter. This should
be not only for the family’s use but to provide guidance to healthcare providers at the onset of illness. The protocol
explains MSUD, its treatment, and emergency procedures. It should be individualized for each patient, give appropriate
demographic and identifying information about the patient, be updated as necessary and provide contact information
for the usual metabolic dietitian and physician.
• At home sick-day diet: minor illnesses can often be handled at home with modifications of the usual diet. Patients and
families should be in contact with their metabolic team and be aware of the clinical signs and symptoms to monitor.
Again, any “sick day” protocol should be updated frequently and individualized for each patient. The typical protocol is
to decrease intact PRO by 50-100% for 24-48 hours, increase medical foods to replace the intact PRO, provide
additional non-PRO energy sources, and ensure adequate fluid intake. If the patient normally supplements with ILE
and/or VAL, this supplementation should continue during this time.
• Illness requiring hospitalization: For ill individuals unable to meet their nutrient requirements orally, hospitalization is
essential. This includes any individual who has a severe concurrent illness/injury requiring specialized medical intervention.
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
15
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Case Studies
CASE 1: A newly diagnosed infant boy
Usage of MSUD Analog (Case report as an example of diet calculation only.)
BB is an 18 day old male infant whose diagnosis was made through newborn screening and confirmatory testing. His
plasma BCAA amino acids have been brought under control with careful management including parenteral feeds,
transition to enteral feeds, and close clinical and biochemical monitoring in a hospital setting. The infant is ready to begin
his “home” diet. Mom has a good breast milk supply and wants to use expressed breast milk as the intact protein source.
BB currently weighs 3.8 kg and is in the 50th percentile for both height and weight. He has a good suck and seems
satisfied on 20 fl oz per 24 hours. As there is a range in the recommendations for the BCAA, energy, and PRO, the initial
recommendation will begin with the midpoint of the recommendations and follow with daily plasma amino acid analyses
and weight gain to guide adjustments.
GOALS (see Table 2 for recommended intakes)
LEU: 266 mg
ILE: 228 mg
VAL: 255 mg
Total PRO: 10 g (can be slightly less than the midpoint of recommendations when breast milk is the source of the intact PRO)
KCAL: 456
Fluid: 600 mL
OTHER DATA for calculations
Breast milk
MSUD Analog
Amount
LEU
ILE
VAL
PRO
KCAL
1 mL
1 mg
0.58 mg
0.56 mg
0.9%
0.6-0.75
1g
0
0
0
0.13
4.75
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Refer back to the steps outlined in the “DIET PRESCRIPTION” section (pg 8). Always begin with meeting the LEU
requirement with intact PRO, then calculate the contribution to the total PRO requirement that is to be met by the medical food.
Summary of diet prescription
AMT
LEU
ILE
VAL
PRO
KCAL
266 mL
266 mg
154 mg
149 mg
2.85 g
192
MSUD Analog
55 g
-
-
-
7.15 g
261
Non-PRO
NA
NA
NA
NA
NA
NA
Supplemental VALa
10.6 mL
-
-
106 mg
-
-
Supplemental ILEa
7.4 mL
-
74 mg
-
-
-
Final volume
600 mL
TOTAL
600 mL/
228 mg
255 mg
10.0 g
453 kcal =
Breast milk
KCAL source
20 fl oz
22 kcal/fl oz
a
1% solutions containing 10 mg/mL
As BB gets older, his diet needs adjustment to account for growth and development. Regular monitoring is essential.
17
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
The choice of medical food depends on, among others, the nutritional needs of the individual, formula access, taste and form
preferences. The following case studies are hence used as examples of diet calculations; other Nutricia products may be
suitable as well. Refer to product overview (Table 3) and detailed nutrition information tables (Appendix 1).
CASE 2: Four year old girl
Usage of MSUD Maxamaid (Case report as an example of diet calculation only.)
LG is a four year old girl who was diagnosed with MSUD as an infant but has had a series of illnesses (chicken pox, strep
throat and otitis media) in the last 18 months that have triggered metabolic decompensation and eventual hospitalization.
Her growth has been impacted by these illnesses and she has gone from a robust child in the 50th percentile for height
and weight to a present height in the 50th percentile and weight in the 25th percentile (100 cm and 14.5 kg, respectively).
She is presently well and her physician has recommended increasing her intake to allow for weight gain. For the past two
years, her plasma BCAA levels (when well) have been in the treatment range when her LEU intake, from intact PRO, was
325 mg per day. In addition, she has required 40 mg supplemental ILE per day, but no supplemental VAL.
GOALS (see Table 2 for recommended intakes)
LEU: 325 mg
ILE: approx 200 mg from fooda plus 40 mg supplemental ILE
VAL: approx 240 mg from fooda
Total PRO: 1.7 x 16 kg (ideal weight) = 29 g
Intact PRO: 5.4 ga
BCAA-free PRO equiv: 23.6 g
KCAL: 70 KCAL x 16 kg (ideal weight) =1120
Fluid: 1400-1600 mL/day
a
These are approximate calculations based on a mixed and varied diet containing, on average:
60 mg LEU
45 mg VAL
37 mg ILE
}
per g PRO
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Refer back to the steps outlined in the “DIET PRESCRIPTION” section (pg 8). Always begin with meeting the LEU
requirement with intact PRO, then calculate the contribution to the total PRO requirement to be met by the medical food.
Summary of diet prescription
AMT
LEU
ILE
VAL
PRO
KCAL
Intact PRO (food)
varies
325 mg
200 mg
243 mg
5.4 g
~650
MSUD Maxamaid
94 g
-
-
-
23.6 g
305
Non-PRO KCAL
source (Duocal )
30 g
-
-
-
-
137
Supplemental VALa
-
-
-
-
-
Supplemental ILEa
4.0 mL
-
40 mg
-
-
-
325 mg
240 mg
243 mg
29 g
~1100 KCAL
®
Final volume
720 mL/24 fl oz
TOTAL
Food+drink
1200 -1600 mL
a
1% solutions containing 10 mg/mL
Two weeks later, plasma BCAA were in the treatment range but analysis of 3-day diet records showed that LG’s intake from food was far
less than the recommended 650 KCAL (although she reached her LEU goal by eating foods with higher LEU content), and she often
consumed all of her medical food by 2 PM each day. She showed no weight gain in the interval. LG’s mother was counseled to spread
the medical food out so that LG had some with each meal and a last serving in the evening. Because LG seemed to want more fluid
during the day, her mother was advised to include a low LEU fruit drink with her snacks. This also provided extra KCAL. Also, guidance
was given to include more fat sources in the diet as analysis showed that LG was getting only about 25 % of her KCAL as fat.
These recommendations were adopted and in two weeks LG showed a weight gain of 0.6 kg. Because she was utilizing the BCAA for
protein synthesis (anabolism), her plasma amino acid analysis indicated that all three BCAA had decreased. LG’s intact PRO
allowance was increased by 10% to: 360 mg LEU or 6.0 g PRO.
LG’s growth, plasma BCAA and dietary intake were closely monitored over the next two months. She returned to and maintained the
50th percentile for both height and weight. Adjustments were made to keep her BCAA within the treatment range.
19
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
CASE 3: A nineteen year old young man
Usage of MSUD Maxamum and MSUD Lophlex LQ (Case report as an example of diet calculation only.)
AM is a nineteen year old male with MSUD who is a college freshman and living in campus housing. At his last clinic visit,
his height was 177 cm and weight 73 kg. He has always done well with maintaining his plasma BCAA in the treatment
range and initiating sick day protocols when ill. He has had a good understanding of the diet calculations and often
prepared an appropriate meal when his parents were not at home. He found that the college cafeteria’s salad/fruit and
dessert bar allowed many choices, and he was able to supplement these with low protein baked goods that he carried in
his backpack when necessary. Approximately three nights a week he prepared a pasta meal in the dormitory kitchen. His
main problem was his medical food. He had been drinking MSUD Maxamum for the last eight years. However, preparing,
storing and carrying the prepared medical food was not convenient for him and many days he consumed as little as 50%
of the prescribed amount. He realized that he was losing weight and his most recent plasma amino acid analysis indicated
that all the BCAA were elevated.
GOALS (diet prescription at the time he left for college)
LEU: 550 mg
ILE: approx 340 mg from fooda
VAL: approx 413 mg from fooda
Total PRO: 1.1 g x 73 kg (ideal weight) = 80 g
Intact PRO: 9.2 ga
BCAA-free PRO equiv: 70.8 g
KCAL: 35 x 73 kg (ideal weight) = 2500
Fluid: ~ 3000 mL/day
a
These are approximate calculations based on a mixed and varied diet containing, on average:
60 mg LEU
45 mg VAL
37 mg ILE
}
per g PRO
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
Refer back to the steps outlined in the “DIET PRESCRIPTION” section (pg 8). Always begin with meeting the LEU
requirement with intact PRO, then calculate the contribution to the total PRO requirement to be met by the medical food.
Summary of diet prescription
Intact PRO (food)
AMT
LEU
ILE
VAL
PRO
KCAL
varies
550 mg
340 mg
413 mg
9.2 g
~1500
Free foods
~450
MSUD Maxamum
177 g
-
-
Supplemental VALa
-
-
-
Supplemental ILEa
-
-
-
550 mg
340 mg
Final volume
-
70.8 g
540
-
-
-
-
-
413 mg
80 g
2500 KCAL
1080 mL/
36 fl oz
TOTAL
2-3000 mL
Food+drink
a
1% solutions containing 10 mg/mL
AM tried the ready-to-drink MSUD Lophlex LQ. He recognized that its small volume and individual serving-sized packaging would
be convenient for his busy life. His insurance company initially denied coverage for this new product. He was able to appeal their
decision with a copy of the product’s nutrition profile (see Table 3 or appendix), and a letter of necessity from his clinic that included
information about his weight loss and rise in BCAA when he was unable to consume all of the MSUD Maxamum.
AM replaced the MSUD Maxamum with 4 servings of MSUD Lophlex LQ. This provided him with 80 g PRO, 480 KCAL and 500
mL fluid. AM was advised that he would need to drink more BCAA-free fluids (approximately 16 fl oz) to replace what he had
been getting in the MSUD Maxamum. AM has found that he can easily do this by mixing one serving of the MSUD Lophlex LQ in
a serving of sweetened beverage when he eats in the cafeteria.
21
GUIDELINES FOR THE NUTRITIONAL MANAGEMENT OF MAPLE SYRUP URINE DISEASE
Appendix 1
MSUD Analog®
Weight, g
Energy, kcals
Protein Equivalent, g
Amino Acids, g
L- Alanine
L-Arginine
L-Aspartic Acid
L-Cystine
L-Glutamic Acid
Glycine
L-Histidine
L-Isoleucine*
L-Leucine*
L-Lysine
L-Methionine
L-Phenylalanine
L-Proline
L-Serine
L-Threonine
L-Tryptophan
L-Tyrosine
L-Valine*
L-Carnitine
Taurine
L-Glutamine
Carbohydrate, g
Fiber, g
Fat, g
Saturates, g
Monosaturates, g
Polyunsaturates,g
Ratio n6: n3 fatty acids
Linoleic Acid, mg
Linolenic Acid, mg
DHA, mg
Vitamins
Vitamin A, IU
Vitamin A, mcg RE
Vitamin D, IU
Vitamin D, mcg
Vitamin E, IU
Vitamin E, mg alpha TE
Vitamin K, mcg
Thiamine, mg
Riboflavin, mg
Vitamin B6, mg
Vitamin B12, mcg
Niacin, mg
Folic Acid, mcg
Pantothenic Acid, mg
Biotin, mcg
Vitamin C, mg
Choline, mg
Inositol, mg
Minerals
Calcium, mg
Phosphorus, mg
Magnesium, mg
Iron, mg
Zinc, mg
Manganese, mg
Copper, mcg
Iodine, mcg
Molybdenum, mcg
Chromium, mcg
Selenium, mcg
Sodium, mg
Potassium, mg
Chloride, mg
100
475
13
MSUD Maxamaid®
100
324
25
MSUD Maxamum®
100.00
305
40
MSUD Lophlex LQ®
125 mL (4.2 fl oz)
120
20
0.76
1.34
1.11
0.49
1.49
1.19
0.76
None
None
1.38
0.32
0.90
1.44
0.89
1
0.40
0.90
None
0.01
0.02
0.10
59
20.9
6.8
9.5
3.6
14.1
3025
230
-
1.48
2.60
2.17
0.96
0.00
2.31
1.49
None
None
2.69
0.63
1.75
2.81
1.73
1.94
0.77
1.75
None
0.02
0.14
1.50
56
<0.1
trace
trace
trace
-
2.40
4.10
3.40
1.60
4.60
3.70
2.30
None
None
4.20
0.99
2.80
4.50
2.80
3.10
1.30
2.80
None
0.04
0.14
0.32
34
<1
trace
trace
trace
-
1.40
1.90
1.45
1.20
0.00
1.90
1.00
None
None
1.78
0.43
1.18
2.38
1.65
1.30
0.53
2.00
None
0.01
0.06
0.00
9.30
0.50
0.44
0.10
0.13
0.21
150
1760
528
340
8.5
4.9
3.3
21
0.5
0.6
0.52
1.25
4.5
38
2.6
26
40
50
100
1665
500
48
12
14.3
9.6
48
0.8
0.8
0.8
2
5
240
3.2
18
62.5
250
56
2228
669
332
8.30
18.3
12.3
82
0.91
0.97
1.6
3.1
5.7
491
4.9
24.5
62
430
80
949
285
320
8.0
4.8
3.2
24.9
0.54
0.50
0.58
1.8
7.1
120
1.8
53.4
17.8
153
40.6
600
500
40
10
8
0.6
450
47
15
15
15
120
420
290
810
810
128
14
11
1.9
1000
144
33
21.5
40
580
840
450
1183
1137
306
14.7
9
1.8
820
131
37
26
58
560
700
560
319
244
96.3
5.1
3.8
0.56
563
56.3
25
10.8
26.8
<25
90
<25
* MSUD Lophlex LQ Juicy Berries may contain traces of leucine, isoleucine and valine from fruit juice (from concentrate) at a level of <1.5 mg/100mL
A PRACTICAL GUIDE FOR THE USE OF NUTRICIA’S MSUD PRODUCTS
23
Guidelines for the Nutritional Management of Maple Syrup Urine Disease
A Practical Guide for the Use off
Nutricia's MSUD Products
For more information or product samples, please visit www.nutricia-na.com
or call
US: (800) 365-7354
Canada: (877) 636-2283
For more tools and resources for the management of your metabolic
patients, please visit www.NutriciaLearningCenter.com