1. Nutrition Management of Maple Syrup Urine Disease

2. Maple syrup urine disease (MSUD) is an inborn error of the branched-chain keto acid dehydrogenase (BCKDH) enzyme complex required for the catabolism of the branched- chain amino acids (BCAA) leucine, valine, and isoleucine

4. Of these, leucine and its corresponding keto acid, 2-oxo-isocaproic acid, are the primary toxic compounds in this disorder.
Infants with severe MSUD come to attention shortly after birth with symptoms such as poor feeding, weak suck, weight loss, and a high- pitched cry progressing to a metabolic intoxication crisis characterized by lethargy, irritability, vomiting, and fluctuating muscle tone(e.g., floppy, then rigid).

5. If the infant is not treated, seizures, metabolic acidosis, coma, and death may result.
There are several classifications of disease severity, including :
Classical
thiamine responsive or intermittent
and mild or variant forms.

6. BCKDH is a thiamine-dependent enzyme, and
individuals with residual enzyme activity may
benefit from thiamine supplementation, but those with classic MSUD do not.

7. Nutrition Management: principles
Restrict : Branched-chain amino acids, especially leucine
Supplement : Valine and isoleucine (if plasma concentrations are below target range), thiamine
Toxic metabolite : Leucine and its keto acid, 2-oxo-isocaproic acid
a Trial of 100–1,000 mg thiamine is completed by some metabolic centers for patients with variant forms of MSUD

8. Initiating Nutrition Management of an Infant with MSUD
Goal : Reduce or normalize plasma leucine Step-by-step :
1. Establish intake goals based on the infant’s diagnostic blood leucine, clinical status, and laboratory values.
2. Determine amount of standard infant formula or breast milk required to meet the infant’s leucine needs. Determine the amount of protein and energy that will be provided by this amount of formula.

9. 3. Subtract the protein provided by the standard infant formula or breast milk from the infant’s total protein needs.
4. Calculate amount of BCAA-free medical food required to meet the remaining protein needs.
5. Calculate valine and isoleucine intake provided by the infant formula/breast milk. Determine the amount of supplemental valine and isoleucine to add to meet recommended intakes (Table ).
The recommended concentration of valine and isoleucine supplements is 10 mg/mL (1 g amino acid in 100 mL water).

10. 6. Determine the number of calories provided by both the infant formula/breast milk and BCAA-free medical food.
If more energy is required, provide the remaining calories from a BCAA-free medical food (as long as the additional medical food does not cause the total protein intake to be excessive).

11. 7. Determine the amount of fluid required to provide a caloric density of 20–25 kcal/oz.
8. Divide total volume into appropriate number of feedings over a 24-h period.

12. Suggested daily nutrient intakes for acutely ill or asymptomatic infants with classic MSUD

13. Once the diet has been established, adjustments in leucine, valine, and isoleucine prescriptions should be based on blood BCAA concentrations rather than maintaining a specific mg/kg intake goal
The amount of the BCAA required per kilogram of body weight decreases as the infant matures.

14. Recommendations for Adjusting the MSUD Diet Prescription
1. Determine the estimated increase or decrease in leucine, isoleucine, and valine intake that will be needed to improve the blood concentrations. Changes in 10 % increments are typical but can be higher or lower based on plasma amino acid concentrations.
2. Adjust the amount of infant formula or breast milk to increase or decrease leucine in the diet.

15. 3. Recalculate the valine and isoleucine content provided by the infant formula or breast milk.
4. Recalculate the amount of supplemental isoleucine and valine needed to meet your intake goals.
5. Recalculate the amount of MSUD medical food required to meet the energy goal.
6. Recheck plasma amino acid concentrations.

16. Solid foods can be introduced to infants with MSUD at the typical age recommended for all infants, unless motor delays are present.
To allow for solid food introduction, the volume of regular infant formula or breast milk is decreased and leucine from these sources is replaced with leucine from solid foods.

17. In MSUD, only the leucine content of foods and beverages need to be counted. There is no need for caregivers to calculate the valine and isoleucine content of foods.
Unless there is a concern about low energy intake, caregivers do not need to count calories from foods or beverages; the medical food provides the majority of energy for infants.

18. Low-protein recipes from cookbooks designed for PKU can be useful for MSUD as well.
The leucine content can be estimated from the protein content of foods (60 mg leucine per gram of protein).
For older individuals with MSUD, counting protein rather than leucine may be appropriate and easier for the patient, if metabolic control can be maintained with this less accurate method.

19. Counting Leucine Intake in the MSUD Diet
Only dietary leucine must be counted
• The valine and isoleucine content of food is about half that of the leucine content.
• Patients will not get too much valine and isoleucine if they consume the prescribed amount of leucine.

20. In patients with classical MSUD, medical foods provide up to 80–90 % of protein needs and a majority of energy needs in infancy and beyond.

21. Recommended blood BCAA concentrations in MSUD
a Recommended maximum blood concentration is
200 μmol/L for infants and children <5 years of age and
300 μmol/L for those >5 years of age

23. Suggested daily nutrient intakes for acutely ill or asymptomatic infants with classic MSUD

25. Step 1: Calculate the amount of each nutrient required each day
Step 1: Calculate the amount of each nutrient required each day. Nutrient goal/kg × Infant weight = daily requirement Leucine: 90 mg/kg × 4 kg = 360 mg/day Isoleucine: 50 mg/kg × 4 kg = 200 mg Valine: 50 mg/kg × 4 kg = 200 mg Protein: 3.0 g protein × 4 kg = 12 g total protein requirement Energy: 110–120 kcal/kg × 4 kg = 440 − 480 kcal/kg

26. Step 2: Calculate amount of standard infant formula needed to meet daily LEU requirement. Amount of LEU required per day ÷ amount of LEU in 100 g of standard infant formula 360 mg ÷ 1,250 mg = × 100 = 29 g standard infant formula needed to meet daily LEU requirement.

27. Step 3: Calculate protein provided from standard infant formula
Step 3: Calculate protein provided from standard infant formula. Amount of standard infant formula × protein provided in 100 g of standard infant formula 0.29 × 10.8 g = 3.1 g protein in standard infant formula

28. Step 4: Calculate the amount of protein required to fill diet prescription Daily protein requirement − protein provided in standard infant formula 12 g − 3.1 g = 8.9 g protein needed to fill in the diet prescription Step 5: Calculate amount of BCAA-free medical food required to fill diet prescription Protein needed to fill diet prescription ÷ protein provided in 100 g of BCAA-free medical food 8.9 g ÷ 13.5 g = × 100 = 66 g BCAA-free medical food required in the diet prescription

29. Step 6: Calculate amount of isoleucine and valine provided from standard infant formula (note: there is no LEU, ILE, or VAL in BCAA-free medical food) Amount of standard formula × ILE in 100 g of standard formula 0.29 × 640 mg ILE = 186 mg ILE Amount of standard formula × VAL in 100 g of standard formula 0.29 × 640 mg VAL = 186 mg VAL

30. Step 7: Calculate the amount of ILE and VAL that needs to be supplemented by an amino acid solution in order to meet the requirements determined in Step 1. ILE: 200 mg − 186 mg = 14 mg ILE to be provided by supplement VAL: 200 mg − 186 mg = 14 mg VAL to be provided by supplement Amino acid solutions can be made to contain 10 mg/mL by adding 1 g (1,000 mg) of amino acid (ILE or VAL) powder to 100 mL 14 mg ILE divided by 10 mg/mL = 1.4 mL ILE solution (containing 10 mg/mL) 14 mg VAL divided by 10 mg/mL = 1.4 mL VAL solution (containing 10 mg/mL)

31. Step 9: Calculate total energy provided from standard infant formula and BCAA-free medical food. Amount of standard infant formula × kcal in 100 g of standard formula × 510 kcal =148 kcal Amount of BCAA-free medical food × kcal of 100 g of BCAA-free medical food × 473 kcal = 312 kcal Add standard formula + BCAA-free medical food for total kcal provided in diet prescription. 148 kcal kcal = 460 kcal

32. Step 10: Calculate the final volume of the formula to make a concentration of 20–25 kcal per ounce. 460 kcal ÷ 20 kcal/oz = 23 oz of formula (Note: if final volume prescribed is 20 oz, caloric concentration will be 23 kcal/oz; if final volume prescribed is 25 oz, caloric concentration will be 18.4 kcal/oz)