1. Phenylketonuria (PKU) disorder and its affects on child and maternal populations

2. Phenylketonuria (PKU) disorder
Phenylketonuria - Understanding PKU
PKU is a genetic disorder in which there is a buildup of Phenylalanine in the body.
Phenylalanine is an essential amino acid, it is contained in a lot of different foods. These include, but are not limited to, fish, pork, cheese, and breast milk.

3. Phenylketonuria (PKU) disorder
Phenylketonuria - Understanding PKU
A person who has PKU lacks a gene which codes for the genetic information on how to synthesis the enzyme phenylalanine hydroxylase, or PAH. This enzyme breaks down the amino acid phenylalanine.
Because of this a person with PKU has to avoid foods containing high amounts of phenylalanine for their entire life.

4. Phenylalanine Hydroxylase
The enzyme works to convert Phenylalanine to another amino acid called tyrosine.
Tyrosine is a precursor to many different hormones. Many of which act as neurotransmitters.
If too much phenylalanine builds up in the body there can be serious health consequences to the brain!

5. Who is at risk for PKU?
PKU is an autosomal recessive disorder. Meaning that two copies of an abnormal gene must be present in order for the disease or trait to develop.
If a child is born and both parents have the same autosomal recessive mutation then there is a 1 in 4 chance of the child inheriting the abnormal gene and inheriting the disease.
Often, the parents will not show signs and symptoms of the condition because they only carry one copy of the mutated gene.

6. Statistics for a child born to a couple who both carry the gene, the expected outcome for each pregnancy is:
A 25% chance that the child is born with two normal genes (normal)
A 50% chance that the child is born with one normal and one abnormal gene (carrier, without disease)
A 25% chance that the child is born with two abnormal genes (at risk for the disease)

7. PKU Testing
Newborn screening- A blood spot test used to screen newborns for the presence of phenylalanine and tyrosine, within 24 hours of life.
Testing during pregnancy- If both gene changes are found in the parents first child, DNA testing can be utilized for future pregnancies. The sample needed for this test is obtained by either CVS (Chorionic Villus Sample) or amniocentesis.
Carrier testing- If both gene changes are found in the parents child then their other family members may be carriers too. DNA testing may be available to them to identify if they are carriers. (PAH Gene Sequencing)
Sequencing of the gene will detect mutations in 99% of individuals with PKU.
Extremely expensive

8. Maternal PKU
Cause:
High phenylalanine levels due to not following diet restrictions. High levels of phenylalanine can reach the fetus and cause:
Low birth weight
Small head (microcephaly)
Heart defects
Increase risk of pregnancy loss

9. PKU In Babies
Untreated PKU in babies can lead to serious health problems such as:
Mental retardation
Delayed cognitive development
Psychiatric disorders: Behavioral, emotional and social problems
Neurological problems possibly leading to seizures
Hyperactivity
Bone density
Bad breath, skin and urine odor, due to increase phenylalanine level
Light skin, blue eyes due to obstruction in phenylalanine transforming to melanin.

10. Children who follow a restricted diet low in phenylalanine can lead normal lives.

11. Objective - To confirm intrauterine growth
Study -- Maternal Phenylketonuria: Low Phenylalaninemia Might Increase The Risk of Intra Uterine Growth Retardation
Background - Malformations and mental retardation in the offspring of women with PKU can be prevented by maintaining maternal blood PHE within a target range ( μmol/L) through a PHE-restricted diet.
Objective - To confirm intrauterine growth
retardation (IUGR) and investigate
its causes

12. Study Continued
Patients French women with PKU pregnant between January 2002 and December 2007
Methods
Weekly PHE blood concentration( µmol/L)
Diet monitoring
3 ultrasound scans during pregnancy
Monthly follow-up
Newborn examination

13. Study Continued Results 91 newborns 17% - low birth weight
40% - low birth length
37% - microcephaly
45% - IUGR
2 cases of CHD - therapeutic abortion

14. Nutritional Management
The diet for PKU was developed in the1960’s
PKU can be managed by a low-phenylalanine diet
It is individualized based on blood phenylalanine response
to protein.
Food to be avoided
Meat, fish, poultry, dairy, soy, legumes (dried beans) or nuts. Some
fruits and vegetables are higher in protein than others.
Food in green have less than 20 mg PHE IN ½ cup serving
Food in yellow have 21.50g PHE per ½ cup per serving.
Food in red should be eaten sparingly, they have mg PHE
per ½ cupt per serving
Classic diet
For the most severe form of PKU.
Eliminate all high protein food.

15. Nutritional Management
Synthetic formula as a nutritional substitute
Uses glycomacropeptide:
A natural protein produced during cheese making
Low PHE when isolated from cheese
Studies in PKU demonstrate that GMP is a nutritionally adequate source of
protein. It improves the metabolic phenotype by reducing concentration
of PHE in plasma and brain.
Should pregnant women with PKU drink milk?
Should a child with PKU be breastfed?
Warning!
Aspartame should be avoided by people with PKU

16. Small changes make a big difference
Higher PHE
Lower PHE
Milk, Half & Half
Rice milk, Non-dairy coffee creamer
Creamy soups
Vegetables soups
Bananas
Apples, grapes, berries
Spaghetti
Bean thread noodles OR Spaghetti Squash
Beef, Poultry
Mushrooms
Mashed potatoes
Mashed cauliflower
Greek yogurt
Coconut based milk and yogurt

17. Prevalence in Ethnicity
PKU is more likely to occur in Ireland, and northern parts of Europe
North America
1 in 50 Caucasians are carriers of PKU
1 in 10,000 to15,000 people in North America have PKU

18. PKU in Europe Thames Region
150,000 births a year are diagnosed with PKU, which is about 1/5 of the annual UK births. This population resides mostly in Europe.
Categories for ethnicity
White
Asian/Asian British
majority of them are from the Indian subcontinent
Black/Black British

19. PKU in Europe Results 167 children (83 boys) have PKU
Majority are white
85.6% white
11.8% mixed
3.0% black/black British or Asian/Asian British