Phenylketonuria (PKU)
By: Adrienne Gebele
What is
1
PKU?
• Inherited disorder
• Occurrence varied due to ethnicity and geography
– About 1 and 10,000 to 15,000 infants are born with in the
U.S.
• People born with PKU have an inactive liver enzyme
which causes a dangerous build up of phenylalanine in
the blood
• To stay healthy a strict low-phenylalanine diet must be
followed
1
Phenylalanine
• An essential amino acid used by the body to
form proteins for growth and tissue repair
• When excess amino acids are consumed they are
chemically changed into other compounds for
energy
• In people with PKU excess phenylalanine builds
up in the blood and affects brain development
PKU & the effect on the brain11:
Phenylalanine
1
Hydroxylase
10
• Normally phenylalanine is converted to tyrosine in
the liver by the enzyme phenylalanine hydroxylase
• Individuals with PKU do not have the enzyme
phenylalanine hydroxylase which results in a
dangerously high build up of phenylalanine
10
Metabolic Pathways :
• Results in low tryosine levels and tryosine
becomes essential to people with PKU5
Genetics
7
•
Autosomal, recessive error of metabolism. 12
•
Mutation of human phenylalanine hydroxylase (PAH), which maps to chromosome
12.15
•
2% chance in N. America if mother is a carrier father will also be a carrier and vise
versa. 10
Registered Dietitian’s
10
Role :
• Provide on going guidance and support
• Introduce complementary foods (eg: solids)
• Implement/change dietary formulas
• Introduce nutrient supplements
• Provide nutrition and disease related
education
20
Registered Dietitian’s Role
Early diagnosis and treatment
lead to excellent cognitive
10
outcomes and brain growth!!
19
6
PKU Symptoms:
• Mental retardation
• Microcephaly
• Behavioral or social problems
• Fair skin and blue eyes
• Seizures, tremors, jerking
movements in the arms and
(phenylalanine cannot
transform into melanin)
legs
• Hyperactivity
• Stunted growth
• Skin rashes (eczema)
• Musty odor in child’s breath,
skin or urine
18
How is it
4
diagnosed?
• Most babies in the U.S. and many other countries are screened
immediately after birth with a blood test.
• Newborns are pricked on heel or hand and the blood is tested for high
phenylalanine levels
• The filter paper with blood on it is placed on a plate of bacteria that can
only grow with phenylalanine
• This test determines now much phenylalanine is in the newborns’ blood.
The bigger halo of bacteria growth means the more phenylalanine is
present in the blood.
• After 2 positive tests a urine and blood test is done to determine if there
is a BH4 deficiency
Ohio Guidelines for
16
PKU :
• Newborn Screening Program
– Currently tests all newborns for 36 disorders after birth.
PKU being one of them.
– PKU and Homocystinuria are treated with special
metabolic formula provided through the Ohio
Department of Health Metabolic Formula Program
– Provides formula to 400 individuals in OH ($600,000 per
year)
9
Common Diagnosis :
• Altered GI function (NC-1.4)
• Altered nutrition-related lab values (NC-2.2)
• Inadequate protein-energy intake (NI-5.3)
• Inadequate fluid intake (NI-3.1)
• Malnutrition (NI-5.2)
How to
•
12
monitor PKU:
Monthly blood phe levels
– Blood phe level= 1-6 mg/dL
– Blood drawn in clinic or filter paper blood sample mailed to lab
•
Regular visits to the PKU clinic
– Nutritional education for patient and parent, support groups, examination by a pediatrician,
blood drawn, management of low-phe food patterns
•
Food Records
– 3 day recall or all food and beverage
– Document protein, energy, vitamins, and minerals
– Formula preparation and consumption
•
Iron status
•
Prealbumin
•
Normal tyrosine blood levels
•
Weight status
The Pediatric Nutrition Care Manual
recommends the following be monitored
for people with PKU15:
• Total energy intake and percentage of energy from
formula/medical food and other foods
• Total protein intake and percentage of total protein from
formula/medical food and other foods
• Phe intake from foods
• Tyrosine intake from medical foods/formula
• Vitamin and mineral intakes (including calcium, iron,
vitamin D, and others) from formula/medical foods and
other foods
PKU is now celebrated as one of
the first human genetic diseases to
have an effective rational therapy.15
8
17
10
7
Food phe levels :
Food
Phenylalanine (mg)
Protein (g)
2% milk (1 cup)
392 mg
8g
Spaghetti (1 cup)
324 mg
6.8 g
Medium egg (1 egg)
300 mg
5.6 g
Vanilla Ice cream (1/2 cup)
210 mg
4.2 g
White bread (1 slice)
140 mg
2.8 g
Cooked brown rice (1/2 cup)
116 mg
2.2 g
Potato (1/2 cup)
75 mg
1.8 g
Mushrooms ( ½ cup)
28 mg
0.7 g
Raisins (1/4 cup)
24 mg
1.2 g
Low Protein white bread (1 slice)
13 mg
0.3 g
Apples (1 cup)
7 mg
0.2 g
Strawberry sorbet (1/2 cup)
6 mg
0.3 g
Margarine (1 Tbsp)
6 mg
0.1 g
Loprofin Macaroni (1 ½ cup)
6 mg
0.2 g
Phenylalanine is in….PROTEIN12
• Fish
• Meat (bacon, beef, turkey, liver, chicken, gelatin)
• Eggs
• Dairy
• Nuts and Legumes
• Soy products (soy protein, tofu, soybean protein)
• Aspartame (Equal, NutraSweet)
• Diet foods & diet sodas
• Gum
• Drugs (Alka-Seltzer and Benadryl)
12
“Special Diet”
• The phenylalanine-free medical food/formula
is the primary source of protein.
• Ensures a person with PKU ingests enough
total protein, energy an nutrient to maintain
appropriate nutrition status and blood phe
levels in the recommended range
5
Low-phe Supplements
13
Phenex-2
-vanilla powder
-serving size: 100g
Sample
20
Menu :
Active Teenager/young adult with PKU:
• Breakfast: 1 cup low-protein cereal with low protein milk substitute
Harifen21 (100ml=9 mg phe), apple, toast (low protein bread) with jelly or
butter, fruit juice/coffee
• Lunch: grilled cheese (low protein bread, low protein cheese), vegetable
soup, fruit juice/coke
• Dinner: Low protein pasta with tomato sauce, salad, buttered toast (low-
protein bread), fruit juice
• Dessert: strawberry sorbet, and fresh strawberries
**Low-Phe supplement 3 times a day (Phenex-2)
– Per serving 410 kcals, 30g protein
12,15
Drug therapy :
• Treatment with BH4
– Kuvan is a form of cofactor for phenylalanine hydroxylase enzyme
called BH4
– Can enhance enzyme activity, lower blood phenylalanine levels,
improve dietary tolerance of phenylalanine.
– Involves activation of phenylalanine oxidation via the PAH enzyme
– Most effective with mild forms of PKU. Not classical PKU.
– Diet will still need to be maintained
– No long term experience with Kuvan. FDA approved based on short
term evidence (26 weeks).
– No obvious “serious adverse effects” have been reported
• Enzyme Therapy15
– Recombinant yeast phenylalanine ammonia lyse (PAL) given orally
or injection
– PAL converts phenylalanine to ammonia and trans-cinnamic acid
– Study shows once a week injections for 12 weeks in a mouse with
PKU the plasma phenylalanine levels dropped to normal levels
• Treatment with large neutral amino acids (LNAA)15
– LNAA is a branched chain neutral amino acid supplement.
– Low phe diet and supplements of LNAAs has reduced
hyperphenylalaninemia by half.
– Phenylalanine is blocked by LNAA so it cannot reach the brain.
– May improve treatment of PKU.
Challenges with having PKU and
living a “normal” life…
Being a teen & living with PKU2
• Tips for eating out with friends
• School Lunches
• Traveling
• Backpack snacks
• PKU accountability pals
• Formula drinking in thermos
• Wisdom teeth
• College bound
PKU &
1
IQ Scores
• IQ scores in individuals with PKU treated shortly after
birth through 12 years of age and keep plasma phe
levels within recommended treatment levels show a
mean of 101 ± 11.
• It is reported that within the first 18 years of life for
each 100 μmol increase in plasma phe concentration
between 394 and 150 μM, there was a 1.3 to 3.9 point
decline in IQ scores.
PKU & Learning
11
Disabilities :
25% of children with early-treated PKU receive stimulant medication for ADHD. 17
PKU and Psychiatric Symptoms11:
Pregnancy with PKU
• High phenylalanine levels during pregnancy is devastating to fetus10
• At risk for having children with microcephaly, congenial heart
disease (CHD), and low birth weight10
• Study6:
– 251 women with classical PKU were prescribed a diet of phe-free
medical food supplements with low-protein foods during their
pregnancy
– Data showed:
• Untreated maternal PKU: 73% microcephaly & 12% CHD
• Prescribed diet maternal PKU: 33.9% microcephaly & 8.8% CHD
Maternal PKU & breastfeeding10
• Breastfeeding should not be a problem for
mothers with PKU
• A low phenylalanine diet is recommended before
the pregnancy, during the pregnancy and during
breastfeeding
• Breast milk still the best source of nutrients for
the infant with a mother with PKU
Breastfeeding an infant with PKU3
• Goal plasma phenylalanine level between 120-400 μmol/l
• If phenylalanine levels are >1200 μmol/l breast feeding is postponed 1-3
days and infant is given a free intake of phe-free formula
• When phenylalanine is reduced by 40-50% the initial value a set amount
of phe-free formula is determined per feeding(65% of total intake) and
breastfeeding without restrictions
• Phe-free formula is reduced 5-15 mL every other day and increase breast
milk
• Normally, day 7-10 infant is discharged and they are intaking 60% breast
milk and 40% phe-free formula.
Breastfeeding & PKU Norway
Study3
• 74 Norwegian PKU infants were breastfed in
combination with a phenylalanine-free formula
• Their weight, length, and head circumference
grew within the normal of range of Norwegian
growth charts
• Phenylalanine blood levels were easily controlled
by 8 days after diagnosis
When living with PKU maintaining
a lower phenylalanine levels by
lifelong nutrition therapy can
have a positive effect on
concentration, mood, attention
which results in improved
cognitive behavior. 10