Transcript PKU Presentation

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
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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.
Statistics for a child born to a
couple who both carry the gene,
the expected outcome for each
pregnancy is:
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A 25% chance that the
child is born with two
normal genes (normal)
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A 50% chance that the
child is born with one
normal and one abnormal
gene (carrier, without
disease)
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A 25% chance that the
child is born with two
abnormal genes (at risk
for the disease)
PKU Testing
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Newborn screening- A blood spot test used to screen newborns for the
presence of phenylalanine and tyrosine, within 24 hours of life.
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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.
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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)
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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:
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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 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 (120300 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 2007
Methods
● 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 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 51-115 mg PHE
per ½ cupt per serving
Classic diet
For the most severe form of PKU.
Eliminate all high protein food.
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
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 America
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1 in 50 Caucasians are carriers of PKU
1 in 10,000 to15,000 people in North America have
PKU
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.
o Categories for ethnicity
▪ White
▪ Asian/Asian British
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majority of them are from the Indian subcontinent
Black/Black British
PKU in Europe
● Results
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167 children (83 boys) have PKU
Majority are white
▪ 85.6% white
▪ 11.8% mixed
▪ 3.0% black/black British or Asian/Asian British