The slides gives you a complete information on the inborn error metabolic disease Phenylketonuria (PKU) its cause, symptoms, mechanism and dietary management.

1. PHENYLKETONURIA
(PKU)
INBORN ERROR METABOLISM
BY: PRAMOD MACHIMADA. A

2. Introduction
■ Phenylketonuria is caused by deficient activity of the enzyme
phenylalanine hydroxylase
■ Phenylalanine hydroxylase is needed to convert the essential
amino acid (AA) phenylalanine (phe) to tyrosine.
■ In order to prevent neurological damage, lifelong adherence
to a low-phe diet that is restricted in natural foods and
requires ingestion of a phe-freeAA formula to meet protein
needs is required.

3. ■ The goal of nutritional management for those with PKU
is to maintain plasma phe concentrations that support
optimal growth, development, and mental functioning
while providing a nutritionally complete diet.
■ Phenylketonuria also called PKU, is a rare inherited
disorder that causes an amino acid called phenylalanine
to build up in the body.

4. ■ PKU is caused by a defect in the PAH gene that create
the enzyme phenylalanine hydroxylase needed to break
down phenylalanine.
■ Without the enzyme a dangerous buildup of
phenylalanine can develop when a person with PKU,
when a person eats foods that contain protein or eats
aspartame, an artificial sweetener.This can eventually
lead to serious health problems.

5. ■ For the rest of their lives, people with PKU — babies,
children and adults — need to follow a diet that limits
phenylalanine, which is found mostly in foods that contain
protein.
■ Phenylketonuria is a genetic disorder inherited from a
person's parents.
■ It is due to mutations in the PAH gene, which results in low
levels of the enzyme phenylalanine hydroxylase.This results
in the buildup of dietary phenylalanine to potentially toxic
levels.

6. Symptoms
■ Newborns with PKU initially don't have any symptoms.
However, without treatment, babies usually develop
signs of PKU within a few months.
■ PKU signs and symptoms can be mild or severe and may
include:
– A musty odor in the breath, skin or urine, caused by too much phenylalanine in the body
– Neurological problems that may include seizures
– Skin rashes (eczema)
– Fair skin and blue eyes, because phenylalanine can't transform into melanin — the pigment responsible
for hair and skin tone
– Abnormally small head (microcephaly)
– Hyperactivity
– Intellectual disability
– Delayed development
– Behavioral, emotional and social problems
– Psychiatric disorders

8. Types of PKU
The severity of PKU depends on the type.
1. Classic PKU
2. Less severe forms of PKU
3. Maternal PKU

9. 1) Classic PKU
■ The most severe form of the disorder is called classic
PKU.
■ The enzyme needed to convert phenylalanine is missing
or severely reduced, resulting in high levels of
phenylalanine and severe brain damage.

10. 2) Less severe forms of PKU
■ In mild or moderate forms, the enzyme retains some
function, so phenylalanine levels are not as high, resulting
in a smaller risk of significant brain damage.
■ But most children with the disorder still require a special
PKU diet to prevent intellectual disability and other
complications

11. 3) Maternal PKU
■ Women who have PKU and become pregnant are at risk
of another form of the condition called maternal PKU.
■ If women don't follow the special PKU diet before and
during pregnancy, blood phenylalanine levels can
become high and harm the developing fetus or cause a
miscarriage.

12. Normal blood phe level: 2mg/dL

13. ■ Babies born to mothers with high phenylalanine levels don't
often inherit PKU.
■ But they can have serious consequences if the level of
phenylalanine is high in the mother's blood during pregnancy.
■ Complications at birth may include:
– Low birth weight
– Delayed development
– Facial abnormalities
– Abnormally small head
– Heart defects and other heart problems
– Intellectual disability
– Behavioral problems

14. Causes
■ A defective gene (PAH genetic mutation) causes PKU,
which can be mild, moderate or severe.
■ In a person with PKU, this defective gene causes a lack of
or deficiency of the enzyme (phenylalanine hydroxylase)
that's needed to process phenylalanine.
■ A dangerous buildup of phenylalanine can develop when
a person with PKU eats protein-rich foods, such as milk,
cheese, nuts or meat, and even grains such as bread and
pasta, or eats aspartame, an artificial sweetener.
■ This buildup of phenylalanine results in damage to nerve
cells in the brain

17. Inheritance
■ For a child to inherit PKU, both the mother and father
must have and pass on the defective gene.This pattern of
inheritance is called autosomal recessive.
■ It's possible for a parent to be a carrier — to have the
defective gene that causes PKU, but not have the
disease.
■ If only one parent has the defective gene, there's no risk
of passing PKU to a child, but it's possible for the child to
be a carrier.
■ Most often, PKU is passed to children by two parents who
are carriers of the disorder.

19. Risk factors
■ Having both parents with a defective gene that causes
PKU- Two parents must pass along a copy of the
defective gene for their child to develop the condition.
■ Being of certain ethnic descent- The gene defect that
causes PKU varies by ethnic groups and it's less common
in African-Americans than in other ethnic groups.

21. Complications
■ Untreated PKU can lead to complications in infants,
children and adults with the disorder.
■ When mothers with PKU have high blood phenylalanine
levels during pregnancy, fetal birth defects or miscarriage
can occur.
■ Untreated PKU can lead to:
– Irreversible brain damage and marked intellectual disability
beginning within the first few months of life
– Neurological problems such as seizures and tremors
– Behavioral, emotional and social problems in older children
and adults
– Major health and developmental problems

24. Prevention
■ If one have PKU and are considering getting pregnant:
– Follow a low-phenylalanine diet- Women with PKU
can prevent birth defects by sticking to or returning to
a low-phenylalanine diet before becoming pregnant.
– Consider genetic counseling-
– If one has PKU, a close relative with PKU or a child with
PKU, may also benefit from genetic counseling before
becoming pregnant.
– Doctor who specializes in medical genetics can help
better understand how PKU is passed through family
tree.

25. Diagnosis
■ Newborn blood testing identifies almost all cases of
phenylketonuria.
■ If one has PKU or a family history of it, doctor may
recommend screening tests before pregnancy or birth.
■ It's possible to identify PKU carriers through a blood test.

26. Testing babies after birth
■ A PKU test is done a day or two after baby's birth.The test is
done after baby is 24 hours old and after baby has ingested
some protein in the diet to ensure accurate results.
■ A nurse or lab technician collects a few drops of blood from
baby's heel or the bend in baby's arm.
■ A laboratory tests the blood sample for certain metabolic
disorders, including PKU.
■ If the indicates baby may have PKU, baby may have additional
tests to confirm the diagnosis, including more blood tests and
urine tests and genetic testing to identify gene mutations

27. Treatment
The main treatment for PKU includes:
■ A lifetime diet with very limited intake of protein, because
foods with protein contain phenylalanine
■ Taking a PKU formula — a special nutritional supplement —
for life to make sure to get enough essential protein (without
phenylalanine) and nutrients that are crucial for growth and
general health
■ A safe amount of phenylalanine differs for each person with
PKU and can vary over time.
■ In general, consume only the amount of phenylalanine that's
necessary for normal growth and body processes, but no
more.

28. Doctor can determine a safe amount through:
■ Regular review of diet records, growth charts and blood
levels of phenylalanine
■ Frequent blood tests that monitor phenylalanine levels as
they change over time, especially during childhood
growth spurts and pregnancy
■ Other tests that assess growth, development and health

29. Formula for people with PKU
■ Because of the restricted diet, people with PKU need to get
essential nutrients through a special nutritional supplement.
■ The phenylalanine-free formula provides protein and other
essential nutrients in a form that's safe for people with PKU.

30. ■ Formula for babies and toddlers-
■ Because regular infant formula and breast milk contain phenylalanine,
babies with PKU instead need to consume a phenylalanine-free infant
formula.
■ A dietitian can carefully calculate the amount of breast milk or regular
formula to be added to the phenylalanine-free formula.
■ Formula for older children and adults-
■ Older children and adults continue to drink or eat a protein substitute
formula daily.
■ Daily dose of formula is divided between meals and snacks, instead of
consumed all at once.
■ It provides essential protein (amino acids) without phenylalanine and
is continued for life.

31. Dietary management
■ The goal of nutritional management for those with PKU
is to maintain plasma phe concentrations that support
optimal growth, development, and mental functioning
while providing a nutritionally complete diet.
■ Natural foods are severely restricted to limit protein
intake yet provide adequate amounts of phe.
■ This generally includes elimination of all sources of
animal protein, legumes and nuts, as well as limited
intake of bread, pasta, rice and some vegetables.

32. ■ Low-protein bread and pasta products made from starch
are used to provide needed energy and to increase
variety.
■ Consumption of an AA-based, phe-free formula (600–900
ml per day) or AA medical food is needed to provide
adequate protein, vitamins, minerals and energy due to
the restriction in natural foods
■ Treatment consists of dietary restriction of phenylalanine
often with tyrosine supplementation.

33. ■ Other essential amino acids are supplemented using various
medical foods, and vitamin, mineral, and other micronutrients
are followed closely.
■ Phenylalanine-restricted diets have been reported to cause
deficiencies of iron, zinc, selenium, and other nutrients and
essential amino acids in patients with PKU.
■ Therefore, the diet requires careful monitoring by a
professional trained in PKU management and frequently
requires supplementation of required nutrients.

34. ■ Phenylalanine levels are followed at regular intervals,
from 1-2 times weekly in neonates to perhaps once per
month in older children and adults.
■ The diet should not be terminated after adolescence,
because strong evidence indicates that
hyperphenylalaninemia can have detrimental effects in
adult patients.
■ Some adults with untreated PKU who have cognitive
decline may show improvement in behavior and physical
manifestations when treated with a phenylalanine-
restricted diet.

35. Foods to avoid
■ Because the amount of phenylalanine that a person with
PKU can safely eat is so low, it's crucial to avoid all high-
protein foods, such as:
– Milk
– Eggs
– Cheese
– Nuts
– Soybeans
– Beans
– Chicken
– Beef
– Pork
– Fish

36. ■ Potatoes, grains and other vegetables that have protein
will likely be limited.
■ Children and adults also need to avoid certain other foods
and beverages, including many diet sodas and other
drinks that contain aspartame. Aspartame is an artificial
sweetener made with phenylalanine.
■ Some medications may contain aspartame and some
vitamins or other supplements may contain amino acids
or skim milk powder.

37. ■ Always check with pharmacist about the contents of
over-the-counter products or prescription medications.
■ The diet means food like meat, fish, poultry, cheese, milk,
bread, chips, pasta, yoghurt, chocolate – things we all
take for granted, are things both children and adults with
PKU either can not have or can only have in very small
measured quantities.

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