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

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.

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.

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!

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.

● 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)

Statistics for a child born to a couple who both carry the gene, the expected outcome for each pregnancy is:

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

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

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.

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

Study -- Maternal Phenylketonuria: Low Phenylalaninemia MightIncrease 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 (120-300 μmol/L) through a PHE-restricted diet.Objective - To confirm intrauterine growth retardation (IUGR) and investigate its causes

Study Continued

Patients - 115 French women with PKU pregnant between January 2002 and December 2007Methods ● Weekly PHE blood concentration(120-300µmol/L)● Diet monitoring● 3 ultrasound scans during pregnancy● Monthly follow-up● Newborn examination

Study Continued

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

Nutritional ManagementThe diet for PKU was developed in the1960’sPKU can be managed by a low-phenylalanine dietIt 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 51-115 mg PHE per ½ cupt per serving Classic dietFor the most severe form of PKU.Eliminate all high protein food.

Nutritional Management

Synthetic formula as a nutritional substituteUses glycomacropeptide:A natural protein produced during cheese making Low PHE when isolated from cheeseStudies 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

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

Prevalence in Ethnicity

● PKU is more likely to occur in Ireland, and northern parts of Europe

● North Americao 1 in 50 Caucasians are carriers of PKUo 1 in 10,000 to15,000 people in North America have

PKU

PKU in Europe

● Thames Regiono 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.

o Categories for ethnicity ▪ White▪ Asian/Asian British

● majority of them are from the Indian subcontinent ▪ Black/Black British

PKU in Europe

● Resultso 167 children (83 boys) have PKUo Majority are white

▪ 85.6% white▪ 11.8% mixed▪ 3.0% black/black British or Asian/Asian British