Download Protein Requirements in Inherited Metabolic Diseases

Protein Requirements
in Inherited Metabolic
Diseases
 For patients with metabolic disorders requiring amino acidbased 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.
 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.
 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Dutch guidelines (2009, unpublished data ) of 2.5 g protein/kg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
 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.
 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.
 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.
 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
 The amount of whole protein consumed per age was 0.92 g/kg
(age3), 0.78 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.
Principles of Nutrition
Management for Phenylketonuria
Restrict : Phenylalanine
Supplement : Tyrosine
Toxic metabolite : Phenylalanine
symptoms
mental retardation
seizures
autistic-like behavior.
Eczema with light hair and light complexion
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.
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.
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.
Frequent monitoring is crucial for the management
of blood phenylalanine concentrations.
There are several ways to initiate the diet depending on the
initial blood phenylalanine concentration.
Wash out period: Complete removal of dietary
phenylalanine
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
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.
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.
 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.
Suggested guidelines to establish the amount
of dietary phenylalanine to introduce into the diet
prescription
Nutrient
blood
Amount of Phe
after the removalDiagnostic
of
phenylalanine
from the diet
phenylalanine
to prescribe after
concentration
“washout” period
(“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
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
Recommended intake for a patient with
PKU
Age
Protein
(g/kg)
Phenylalanine Phenylalanine Tyrosine
(mg/kg)
(mg/day)
(mg/kg)
Tyrosine
(mg/day)
Birth to 3
months
3.0–3.5
25–70
130–430
300–350
1,100–1,300
3 to <6
months
3.0–3.5
20–45
135–400
300–350
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
2.5–3.0
10–35
135–330
250–300
2,500–3,000
1 to 7 years
≥30 g
-
200–400
-
2,800–3,500
Energy requirement
Age
Energy requirement(Cal/kg/day)
0-6 months
110
6–12 months
100
1–3 years
90
3–6 years
80
6–12 years
65
12–15 years
50
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.
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.
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.
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.
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.
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.
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.
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.
 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
 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
0
1440
13.5
473
Enfamil
Premium
powder
100 g
430
500
10.8
510
 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.
 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
 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
 Step 6: Calculate amount of tyrosine provided from standard infant formula and Phefree 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 + 806 mg = 1,016 mg
 1,016 mg/4 kg = 254 mg Tyr/kg
 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 + 265 kcal = 479 kcal
 479 kcal/4 kg = 120 kcal/kg
 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 = 23.95 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)