1. Protein Requirements in Inherited Metabolic Diseases

2. For patients with metabolic disorders requiring amino acid- based metabolic formulas, the RDA may not be the best indicator for protein adequacy because nitrogen balance studies that determine requirements are based on healthy individuals.

3. The optimal amount of protein to provide to patients with metabolic disorders is not well established.
the current WHO recommendation is 0.9 g/kg of protein versus the updated guidelines for PKU that recommend an intake of 2.5–3.5 g of protein per kilogram of body weight.
Risk of protein over-restriction is a serious concern and can lead to protein-energy malnutrition and poor growth
In contrast, too much protein may be contraindicated and result in metabolic decomposition and worse.

4. Traditionally in the United States, the recommended protein intakes for infants with PKU an other inborn errors of metabolism range from 3.0 to 3.5 g/kg body weight or higher which is significantly greater than the DRIs for age
recommendation for adults protein intakes closer to the RDA with an added safety factor of 120–140 %
For infants, the new recommended intakes are more in line with Dutch guidelines (2009, unpublished data ) of 2.5 g protein/kg body weight

5. In inherited metabolic disorders, not only is total protein a major consideration, but also the balance of individual amino acids.
Excessive or imbalanced plasma amino acid concentrations negatively affect absorption, protein synthesis, and brain concentrations of indispensable amino acids.

6. Providing sufficient protein and energy in patients with severe metabolic disorders, such as organic acidemias, can be a challenge in maintaining optimal nutrition status.
Failure to thrive, anorexia, compromised immune functions, vomiting/ diarrhea, and metabolic decompensation are not uncommon.
Severe feeding difficulties are also common.

7. The foundation of nutrition management is a moderate protein, moderate energy (mostly in non- or limited-ambulatory patients) to promote anabolism.
The exact amount of restricted indispensable amino acids and whole protein is determined by age, disease severity, blood analytes, and growth rate.

8. The incidence of PKU in those of Northern European descent is approximately 1 in 10,000 births with varying incidences in other populations
PKU is inherited in an autosomal recessive pattern. Both parents carry the gene for PKU but do not show any signs of the disorder.
With each pregnancy there is a 25 % chance of having a child affected by PKU.
Over 500 mutations have been described in the PAH gene

9. The amount of whole protein consumed per age was 0. 92 g/kg (age3), 0
The amount of whole protein consumed per age was 0.92 g/kg (age3), g/kg (age 6), and 0.77 g/kg at 11 years of nutrition management.
Most patients suffered from feeding disorders, and many were given nocturnal feedings.

10. Principles of Nutrition Management for Phenylketonuria Restrict : Phenylalanine Supplement : Tyrosine Toxic metabolite : Phenylalanine

11. symptoms mental retardation seizures autistic-like behavior.
Eczema with light hair and light complexion

12. Nutrition Management
Diet treatment for PKU includes a diet restricted in phenylalanine and an amino acid-based medical food devoid of phenylalanine.
Medical foods for PKU provide all other indispensable amino acids, tyrosine, fat, carbohydrate, and micronutrients.
The amino acids in medical foods provide the majority of protein for patients with PKU.
The amount of intact protein required to meet phenylalanine needs is often so limited that, without use of a medical food, protein deficiency would develop.

13. Nutrition Management
Tetrahydrobiopterin (BH 4 ) is the cofactor for the enzyme PAH.
Nearly 50 % of individuals with PKU are “responders” to the prescription form of BH 4.

14. When an infant is referred to a metabolic clinic with PKU:
the first step is to reduce the blood phenylalanine concentration into the treatment range of 120–360 μmol/L (2–6 mg/dL).
Once the blood phenylalanine concentration trends down toward treatment range, a source of intact protein is added to provide the infant’s phenylalanine needs.

15. Frequent monitoring is crucial for the management of blood phenylalanine concentrations.

16. There are several ways to initiate the diet depending on the initial blood phenylalanine concentration.
Wash out period: Complete removal of dietary phenylalanine

17. Suggested Time Frame for Initial Removal of Phenylalanine from the Diet
Diagnostic Phe concentration
Remove dietary Phe for (h)
360–600 μmol/L (6–10 mg/dL) 24
600–1,200 μmol/L (10–20 mg/dL) 48
1,200–2,400 μmol/L (20–40 mg/dL) 72
>2,400 μmol/L (>40 mg/dL) 96

18. For those with lower initial phenylalanine concentrations, it may be prudent to initially prescribe 25–50 % of estimated phenylalanine needs to avoid decreasing the blood concentration below the treatment range.

19. Once the blood phenylalanine concentration is close to or within the treatment range, the next step is to add a calculated amount of standard proprietary infant formula or breast milk to the phenylalanine PKU medical food to provide the estimated phenylalanine needs of the infant.

20. The range of dietary phenylalanine required by an infant is 130–430 mg/day.
Exactly how much phenylalanine to prescribe after the initial “washout period” is a matter of judgment – often those with higher initial blood phenylalanine concentrations require less phenylalanine introduced into the diet.
For example, an infant with an initial blood phenylalanine concentration of 1,600 μmol/L may be prescribed 45 mg/Kg of phenylalanine after the recommended 72-h washout period whereas an infant with an initial blood phenylalanine concentration of 900 μmol/L would be prescribed 55 mg/Kg of phenylalanine after the suggested washout period of 48 h.

21. Suggested guidelines to establish the amount of dietary phenylalanine to introduce into the diet prescription after the removal of phenylalanine from the diet (“washout period”)
Nutrient
Diagnostic blood
phenylalanine
concentration
Amount of Phe
to prescribe after
“washout” period
(mg/kg)
Phenylalanine
<600 μmol/L
(<10 mg/dL) 70
600–1,200 μmol/L
(10–20 mg/dL) 55
1,200–1,800 μmol/L
(20–30 mg/dL) 45
1,800–2,400 μmol/L
(30–40 mg/dL) 35

22. Comparison of nutrients in a typical standard infant formula and mature breast milk
In 100 ml
(standard dilution)
Infant
formula
Breast
milk – mature
Phenylalanine
60 mg
46 mg
Tyrosine
58 mg
53 mg
Protein
1.4 g
1.05 g
Energy
68 Kcal
70 Kcal

23. Recommended intake for a patient with PKU
Age
Protein
(g/kg)
Phenylalanine
(mg/kg)
(mg/day)
Tyrosine
Birth to 3 months
3.0–3.5
25–70
130–430
300–350
1,100–1,300
3 to <6 months
20–45
135–400
1,400–2,100
6 to <9 months
2.5–3.0
15–35
145–370
250–300
2,500–3,000
9 to <12 months
10–35
135–330
1 to 7 years
≥30 g -
200–400
2,800–3,500

24. Energy requirement Age Energy requirement(Cal/kg/day) 0-6 months 110
100
1–3 years 90
3–6 years 80
6–12 years 65
12–15 years 50

25. Initiating Nutrition Management of an Infant with PKU (Using Standard Infant Formula as the Source of Phenylalanine)
Goal : Reduce plasma phenylalanine concentrations to between 120 and 360 μmol/L.
1. Establish intake goals based on the infant’s diagnostic blood phenylalanine, clinical status, and laboratory values.
2. Determine amount of standard infant formula required to provide the amount of phenylalanine required to meet the infant’s needs. Determine the amount of protein and energy that will be provided by this amount of formula.

26. 3. Subtract the protein provided by the standard infant formula from the infant’s total protein needs. Calculate amount of phenylalanine-free medical food required to meet the remaining protein needs.

27. 4. Determine the number of calories provided by both the infant formula and phenylalanine- free medical food. Provide the remaining calories from a phenylalanine- free medical food.
5. Calculate amount of tyrosine provided by both the infant formula and phenylalanine- free medical food.

28. 6. Determine the amount of fluid required to provide a caloric density of 20–25 kcal/oz.
7. Divide this volume of medical food into feedings for a 24-h period.

29. Initiating Nutrition Managemen of an Infant with PKU (Using Breast Milk as the Source of Phenylalanine)
Goal : Reduce plasma phenylalanine concentrations to between 120 and 360 μmol/L.
1. Establish intake goals based on the infant’s diagnostic blood phenylalanine, clinical status, and laboratory values.
2. Determine amount of breast milk required to provide the infant’s estimated phenylalanine needs. Determine the amount of protein and energy that will be provided by this volume of breast milk.

30. 3. Subtract the calories provided by the breast milk from the infant’s total energy needs.
4. Subtract the protein provided by the breast milk from the infant’s total protein needs. Calculate amount of phenylalanine- free medical food required to meet the remaining protein requirement.

31. 5. Determine the number of calories provided by both the breast milk and phenylalanine- free medical food. Provide the remaining calories from additional phenylalanine-free medical food.
6. Calculate amount of tyrosine provided by both the breast milk and phenylalanine- free medical food.
7. Determine the amount of fluid required to provide a 20 kcal/oz formula.

32. Patient History
A newborn infant tested positive for PKU upon newborn screening.
The initial blood phenylalanine concentration was 1,800 μmol/L (30 mg/dL).
Based on this result, all phenylalanine was removed from the diet for 72 h (“wash-out” period).
The infant is now 10 days old and the most recent blood phenylalanine concentration is 600 μmol/L (10 mg/dL) and phenylalanine needs to be re-introduced into the diet.
Based on the blood phenylalanine concentration at newborn screening (1,800 μmol/L), the recommended amount of phenylalanine to introduce into the diet is 45 mg/kg.

33. Ten (10) day old infant male weighing 4
Ten (10) day old infant male weighing 4.0 kg who was diagnosed with PKU based on elevated blood phenylalanine concentrations.
Patient is doing well and currently drinking 22 oz of PKU Periflex ® Early Years formula
Nutrient intake goals(per day):
Phenylalanine: 45 mg/kg (range 25–70 mg/kg or 130–430 mg/d)
Protein: 3.0 g/kg (range 3.0–3.5 g/kg)
Tyrosine: 300–350 mg/kg
Energy: 100–120 kcal/kg
Fluid: 150 mL/kg
Recommended caloric density of formula: 20–25 kcal/oz

34. Select nutrient composition of formulas for PKU diet calculation example (using standard infant formula as the source of whole protein)
Medical food
Amount
PHE (mg)
TYR (mg)
PROTEIN (g)
ENERGY (kcal)
PKU
Periflex Early Years
100 g
1440
13.5
473
Enfamil Premium
powder
430
500
10.8
510

35. Step 1: Calculate the amount of Phe required each day.
Phe Goal × Infant Weight = mg Phe per day
45 mg Phe × 4 kg = 180 mg/day Phe
Step 2: Calculate amount of standard infant formula needed to meet daily Phe requirement.
Amount of Phe required per day ÷ Amount of Phe in 100 g of standard infant formula
180 mg Phe ÷ 430 mg Phe = 0.42
0.42 × 100 = 42 g standard infant formula needed to meet daily Phe requirement.

36. Step 3: Calculate protein and energy provided from standard infant formula.
Amount of standard formula × protein provided in 100 g of standard formula
42 × 10.8 g protein = 4.5 g protein in standard infant formula
Step 4: Calculate amount of protein to fill the diet prescription.
Protein goal x Infant weight = daily protein requirement
3.0 g protein × 4 kg = 12 g daily protein requirement
Daily protein requirement − protein provided by standard infant formula
12 g − 4.5 g = 7.5 g protein needed from medical food to fill in the diet prescription

37. Step 5: Calculate amount of protein required from Phe-free medical food.
Protein needed to fill prescription ÷ protein provided in 100 g of medical food
7.5 g ÷ 13.5 g = 0.56
0.56 × 100 = 56 g Phe-free medical food required to fill the diet prescription

38. Step 6: Calculate amount of tyrosine provided from standard infant formula and Phe- free medical food.
Amount of standard formula × Tyr in 100 g of standard formula
0.42 × 500 mg Tyr = 210 mg Tyr
Amount of Phe-free medical food × Tyr in 100 g of Phe-free medical food
0.56 × 1,440 mg Tyr = 806 mg Tyr
Add standard formula + Phe-free medical food for total Tyr provided in diet prescription.
210 mg mg = 1,016 mg
1,016 mg/4 kg = 254 mg Tyr/kg

39. Step 7: Calculate total energy provided from standard infant formula and Phe-free medical food.
Amount of standard infant formula × kcal in 100 g of standard formula.
0.42 × 510 kcal = 214 kcal
Amount of phe-free medical food × kcal of 100 g of phe-free medical food.
0.56 × 473 kcal = 265 kcal
Add standard formula + Phe-free medical food for total kcal provided in diet
prescription.
214 kcal kcal = 479 kcal
479 kcal/4 kg = 120 kcal/kg

40. Step 8: Calculate the final volume of formula to make a concentration of 20 kcal per ounce.
Amount of total calories provided by diet prescription ÷ 20 fluid ounces = number of
ounces of formula needed to provide caloric concentration of 20 kcal/oz
479 kcal ÷ 20 kcal/oz = oz of formula
(Note: If final volume prescribed is 24 oz, caloric concentration will be 20 kcal/oz; if final volume prescribed is 23 oz caloric concentration will be 20.8 kcal/oz- either is acceptable)