PHENYLKETONURIA Chelsea Amman, Dietetic

Intern
Case Study
(PKU) June 2017
OBJECTIVES
1. Define Phenylketonuria and how it is
diagnosed
2. Name one nutrition related intervention for
people with PKU (infants or adults)
3. List two side effects of PKU if
untreated/unmanaged
4. Understand the role of the RD in PKU
management
PATIENT PROFILE
Female
7 months old
Lives with mom and dad
Loves scooting around, eating, and is working on crawling
Diagnosis: Phenylketonuria (PKU), admitted for monitoring
of potentially elevated phenylalanine levels
CASE STUDY MEDICAL
HISTORY AND DIAGNOSIS
Birth
Full term
Gestational age: 37-41 weeks
Birth weight: 8 pounds
Birth length: 20.5 inches
Delivery method: vaginal
Hyperbilirubinemia during the newborn period phototherapy was
provided
CASE STUDY PATIENT -
FOOD AND NUTRITION
RELATED HISTORY
Typical intake breast milk, phenylalanine free formula, and
initiation of baby food
No previous diet therapy prior to PKU management
Diet Prescription: Protein controlled diet, Phe free formula diet
was initiated on day 7 of life
 ANTHROPOMETRICS/PERTIN
ENT LABS
Based on WHO growth charts 2/7/17 7/20/16 6/22/16

Weight: 11.1 kg (>98th percentile) Phe 557 268 3,178

umol/L umol/L umol/L
Length/Height: 68.5 cm (50th (9mg/dL (4mg/dL (52mg/d
) (high) ) (high) L)(high)
percentile)
Weight for length/BMI (percentile):
>98th percentile
Previous Weight: 6.4 kg
Ideal body weight: 7.6 kg
% Ideal body weight: 146%
NUTRITION DIAGNOSIS
Impaired nutrient utilization (phenylalanine) related to diagnosis
of phenylketonuria as evidenced by a positive newborn screening
and confirmatory testing, and the need for phenylalanine restricted
diet
Excessive growth rate related to increased intake from foods as
evidenced by a growth velocity of 1100 grams per month
PHENYLALANINE (PHE)
Essential Amino Acid (need to obtain it from food)
Too much or too little is harmful, but it is necessary to have
some
Precursor for Tyrosine (Needs phenylalanine hydroxylase
and BH4)
Found naturally in breast milk, eggs, chicken, beef, and
other foods that are considered protein sources
WHAT IS PKU?
An inherited disorder of amino acid metabolism specifically Phenylalanine (Phe)
the body is deficient in the enzyme phenylalanine hydroxylase (PAH made in the
liver), which is responsible for breaking down Phe into Tyrosine
The result is abnormal build up of Phe in the blood, which is then carried to the
brain, and can lead to central nervous system damage

Autosomal recessive trait (both parents are carriers)

Possible to have one child with PKU, and another without

PKU is not something a person can outgrow, and it is not contagious

NORMAL PATHWAY

PAH
PKU PATHWAY

PAH
SIDE EFFECTS OF
UNTREATED/UNMANAGED
PKU
Mental retardation
Seizures
Hyperactivity/Behavior Issues
Restlessness and irritability
Eczema
Musty or mousy odor
Fair hair and skin
Psychological problems
PKU CLASSIFICATIONS
Classic PKU: 20-40+ mg/dL (1200 2400+ umol/L) Phe
Most common form of PKU
Little to no PAH enzyme activity
Mild PKU: 6-20 mg/dL (360-1200 umol/L) Phe
Phe levels are still elevated, but less so than in Classic PKU
Hyperphenylalanemia (HyperPhe): 2-6 mg/dL (120 - 360
umol/L) Phe
Blood phe levels are above normal, but may not require dietary
treatment

RECOMMENDED PHE LEVELS

FOR PEOPLE WITH PKU
Age Blood Phe level

<12 years 2-6 mg/dL

>12 years (male) 2-6 mg/dL

>12 years (female) 2-6 mg/dL

Maternal 2-4 mg/dL

NEWBORN SCREENING
PKU is an inherited disorder and cannot be prevented, but the
negative complications from uncontrolled PKU can be
Newborn screening for PKU began in 1965
No informed consent is required and in Michigan it is considered a
misdemeanor to skip newborn testing
Specimens are tested the day that they arrive, with some results
communicated the same day
Confirmatory testing at a qualified facility must be done after a
positive newborn screen
CASE STUDY MEDICAL
HISTORY AND DIAGNOSIS
36 hour Newborn Screen was positive for PKU
Phenylalanine (Phe) level: 11.4 mg/dL (Normal <1.5 mg/dL)
Phe to Tyrosine Ratio: 11mg/dL (Normal <1.5 mg/dL)

Confirmatory Testing on 6/22/16

Phe level: 52.44 mg/dL
CURRENT MEDICAL
TREATMENT
Kuvan (sapropterin, sapropterin dihydrochloride)
Synthetic form of the BH4 co-factor
Helps to stimulate activity of any residual PAH
Not every PKU patient responds to treatment
CURRENT MEDICAL
TREATMENT
Large Neutral Amino Acids (LNAA)
Considered medical food/product
Used for adults experiencing difficulty with control of Phe
LNAA pills have higher concentrations of amino acids that
compete with Phe
Taken with food
Competing amino acids to cross the blood brain barrier
CURRENT PKU NUTRITION
TREATMENT
Patients must follow this diet for life
First nutrition intervention: Initiation of Phe-free formula (duration
depends on initial Phe Level)
Home monitoring blood spots, emails, phone calls directly with
dietitians
Avoidance of higher protein foods (once able to eat)
Individualization of diets based on patient/parent preferences
Diet mainly consists of fruits, vegetables, fats, and special low
protein medical foods
Phe tolerance CAN change as patients age, this is why diet diaries
CASE STUDY PATIENT -
INITIAL NUTRITION THERAPY
Formula: Phenex 1(Phe free formula, 20 kcals/ounce)
FIRST 98 HOURS: ONLY Phenex 1 formula, with a blood spot to be
taken after 48, and then 96 hours
After the initial 98 hour period:12 ounces (6 tablespoons) Phenex 1
per day, with the remainder of feedings being at the breast
The 12 ounces should be spread throughout the day, possibly 1-2
tablespoons before feedings
Another blood spot is to be taken 24 hours after the reintroduction
of breast milk into the diet
Detailed diet records are encouraged, and blood spots are to be
mailed in
CASE STUDY PATIENT
ESTIMATED NUTRIENT
NEEDS
Estimated Nutrient Needs: 910 calories per day (EER
sedentary/low active), 22-27 grams total protein (2-2.5 g/kg)
Estimated protein from food (based on recall Mom just started
introducing baby foods): 1.5 grams
The rest of the protein will come from the remaining breast milk
Age Phe Tyr Protein Energy (kcal/kg)*
(mg/kg) (mg/kg) (g/kg)
Infants
0 to <3 25-70 300-350 3.50-3.00 120 (145-95)
months
3 to <6 20-45 300-350 3.50-3.00 120 (145-95)
months
6 to <9 15-35 250-300 3.00-2.50 110 (135-80)
months
9 to <12 10-35 250-300 3.00-2.50 105 (135-80)
months
Girls and (mg/day) (g/day) (g/day) (kcal/day)
Boys
1 to <4 200-400 1.72-3.00 >30 1300 (900-1800)
years
4 to <7 210-450 2.25-3.50 >35 1700 (1300-2300)
years
7 to <11 220-500 2.55-4.00 >40 2400 (1650-3300)
years
 Age Phe Tyr (g/day) Protein Energy*
(mg/day) (g/day) (kcal/day)
Women
11 to <15 250-750 3.45-5.00 >50 2200 (1200-
years 3000)
15 to <19 230-700 3.45 5.00 >55 2100 (1200-
years 3000)
> 19 years 220-700 3.75-5.00 >60 2100 (1400-
2500)
Men
11 to <15 225-900 3.38-5.50 >55 2700 (2000-
years 3700)
15 to <19 295-1100 4.42-6.50 >65 2800 (2100-
years 3900)
>19 years 290-1200 4.35-6.50 >70 2900 (2000-
3000)

* Dietitians at the DMC use the Texas

Childrens book for calories, but this chart
from Metabolic University for protein and
DIET CHANGES
Date Calorie and Diet Provides
Protein Needs
7/21/2016 495 calories (110 14 oz breastmilk 493 calories,
kcal/kg/day), + 1/3 cup and 1 10.43 grams
13.8-16.1 grams tbsp. Phenex 1 + protein, 194.8
protein (3 water to make 21 mg Phe
grams/kg/day) ounces
9/29/2016 652.8 calories 21 ounces 711.6 calories,
(102 breastmilk + 14.8 grams
kcal/kg/day), 16- cup and 3 tbsp. protein, 291.9
19.2 grams Phenex 1 + mg Phe
protein (2.5-3 water to make 26
grams/kg/day) ounces
10/14/2016 Modification due 686 calories,
to high Phe level 15.46 grams
17 oz breast protein, 231.9
milk + cup and mg Phe
DIET CHANGES
Date Calorie and Diet Provides
Protein needs
2/7/2017 910 calories (EER), 6 oz breast milk + 561.4 calories,
22-27 grams total cup Phenex 1 in 15.42 grams
protein 28 ounces final protein, 83.4 mg
volume + Baby Phe
Food
Patient is now
taking in 1.5 grams
protein from food
2/9/2017 910 calories, 22-27 4 ounces breast Provides similar
grams total protein milk + cup needs as above
Phenex 1 + water with a more
to make 25 ounces concentrated
+ 1.5-2 grams formula
protein from
TECHNOLOGY AND
MANAGEMENT
Mail, Email, and telehealth are very important
Blood spots
Weekly testing on the patients heel
Test is done 3-3.5 hours after oral intake
All blood spots are to be sent with at least a three day diet diary
RDs receive diet diaries and Phe level results from blood spot
testing, diets are modified from there
Families and/or patients are contacted as soon as possible to
review and make changes
PKU DIET
1 gram of protein = 50 mg Phe
Example: 4 grams of protein in a food
4 grams protein x 50 mg Phe/1gram protein = 200 mg Phe
Requires counting of protein for everything, including foods like
juice and vegetables with limited amounts of Phe
Ratio is not always accurate based on How Much Phe? Database -
tends to overestimate Phe content
Patients are given a protein or Phe limit
 Never Foods: cheese, eggs,
SIMPLIFIED PKU DIET meat, fish, poultry, animal
based milk and dairy products,
soy products

Free Foods (1/2 cup Limited Foods (1/2 cup Very Limited Foods (1/2
serving) serving) Count grams cup serving) count
of protein grams of protein
All fruit, except dried Artichokes Beans
Fruit Juices Arugula Hummus
Popsicles Asparagus Regular bread products
All Vegetables, except Avocado/guacamole (including bagels and
those in other columns Corn muffins)
All low protein medical Dried fruit (1/4 cup) Dairy free cheese
foods Potatoes Granola bars
All condiments, except Peas Nuts and nut butters
soy based sauces Spinach Pastries, donuts
Coconut, flax, rice, and Sweet potatoes Rice
almond milk (that have 0 Whole grain cereals
grams protein)
PRODUCTS AND FOODS
Medical formula provides all essential amino acids except for Phe, as
well as vitamins and minerals that kids who do not have PKU would
get from their diet
Formulas:
Phenyl Free 2 (Mead Johnson)
Phenex 2 (Abbot)
Periflex Jr. and Advance (Nutricia)
LowPhlex (Nutricia)
PKU Express and Express Coolers (Vitaflo)
MEDICAL FOODS
Low protein foods and formulas created for people with PKU
Cambrooke
- low protein, PKU appropriate varieties of many different foods
- hamburgers, crackers, chicken patties, pasta, etc.
CASEIN
GLYCOMACROPEPTIDE
(CGMP-AA) POTENTIAL
ALTERNATIVE?
Issues with compliance as patients age, taste of products is
a major factor!
CGMP-AAs contain residual amounts of Phe
Study published in 2017 looked at the affect of residual Phe
on overall control of Phe levels
Determined that Phe levels could be controlled
Patients reported increased satisfaction in taste
Increased chance of compliance as patients age

This PKU treatment requires close monitoring

OUTCOMES FOR PEOPLE
WITH CONTROLLED PKU
Normal cognitive function prevented neurotoxicity
Normal growth and development
- Study from 2014: New insights in growth of phenylketonuric
patients found that a normal growth can be achieved with dietary
treatment in PKU patients
Improved behavior
Some issues with obesity, especially in the female population as
they age
Dental caries can be an issue
CONTROLLING PKU
EMOTIONAL TOLL
Assessment of the impact of phenylketonuria and its
treatment on quality of life of patients and parents from
seven European countries. A 2015 study
The highest PKU-QOL impact scores (indicating greater impact)
were for emotional impact of PKU, anxiety about blood Phe levels,
guilt regarding poor adherence to dietary restrictions or Phe-free
amino acid supplement intake and anxiety regarding blood Phe
levels
CASE STUDY PATIENT
CURRENT OUTCOMES
Normal cognitive functioning so far no neurological deficits were
noted based on physician examination
Previous to this admission, growth was normal
Weight gain attributed to increased appetite without increased
movement (patient was still figuring out how to crawl)
Case Study Patients mother felt comfortable with the RDs and was
able to introduce baby food at a normal time in the patients life
PERSONAL
REACTIONS/CONCLUSION
PKU was interesting to me because of the level of RD involvement
This disease cannot be managed properly without frequent
nutrition intervention
The diet is for life, and RDs are currently working to find realistic
nutrition interventions to help patients find ways to comply for life
QUESTIONS?
REFERENCES
Glycomacropeptide in children with phenylketonuria: does its phenylalanine content affect
blood phenylalanine control?: https://www.ncbi.nlm.nih.gov/pubmed/28111827
New insights in growth of phenylketouric patients: Couce, M.L., Guler, I., Anca-Couce, A. et al.
Eur J Pediatr (2015) 174: 651. doi:10.1007/s00431-014-2446-8
https://link-springer-com.sladenlibrary.hfhs.org/article/10.1007/s00431-014-2446-8
Assessment of the impact of phenylketonuria and its treatment on quality of life of patients
and parents from seven European countries:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626680/
http://www.cambrooke.com/
http://www.medicalfood.com/
Nutrition Management of Inherited Metabolic Diseases: Lessons from Metabolic University
Laurie E. Bernstein, Fran Rohr, Johanna R. Helm
Simplified Diet resources with permission from the DMC Metabolic Clinic