Phenylketonuria is a disorder of amino acid metabolism that occurs in infants born without the

ability to normally break down an amino acid called phenylalanine. Phenylalanine, which is
toxic to the brain, builds up in the blood. Phenylketonuria occurs when parents pass the defective
gene that causes this disorder on to their children.

 Phenylketonuria is caused by a lack of the enzyme needed to convert phenylalanine to

tyrosine.
 Symptoms include intellectual disability, seizures, nausea, vomiting, an eczema-like rash,
and a mousy or musty body odor.
 The diagnosis is based on a blood test.
 Children who are diagnosed and treated early should develop normally.
 A strict phenylalanine-restricted diet allows for normal growth and development.

Phenylketonuria (PKU) is a disorder that causes a buildup of the amino acid phenylalanine,
which is an essential amino acid (one that cannot be made in the body but must be consumed in
food). Excess phenylalanine is normally converted to tyrosine, another amino acid, and
eliminated from the body. Without the enzyme that converts it to tyrosine, called phenylalanine
hydroxylase, phenylalanine builds up in the blood and is toxic to the brain, causing intellectual
disability.

Symptoms
Newborns with PKU rarely have symptoms right away, although sometimes they are sleepy or
eat poorly. Symptoms develop slowly over several months as phenylalanine builds up in the
blood. If not treated, affected infants progressively develop intellectual disability over the first
few years of life, which eventually becomes severe. Other symptoms include

 Seizures
 Nausea and vomiting
 Eczema-like rash
 Lighter skin, eye, and hair color than their family members
 Aggressive or self-injurious behavior
 Hyperactivity
 Sometimes psychiatric symptoms

Untreated children with phenylketonuria often give off a mousy or musty body odor as a result of
a by-product of phenylalanine (phenylacetic acid) in their urine and sweat.

Diagnosis
 Newborn screening test
 Prenatal screening tests

Phenylketonuria is usually diagnosed with a routine newborn screening test.

PKU occurs in most ethnic groups. If PKU runs in the family and DNA is available from an
affected family member, the prenatal screening tests amniocentesis or chorionic villus sampling
with analysis of DNA (the building blocks of genes) can be done to determine whether a fetus
has the disorder.

Parents and siblings of children with PKU can be tested to find out whether they carry the gene
that causes the disease. If two carriers conceive a child, that child has a 1 in 4 chance of being
born with the disease. Carriers are people who have an abnormal gene for a disorder but who do
not have symptoms or visible evidence of the disorder.

Prognosis
Children who are treated in the first few days of life do not develop any symptoms or
complications of phenylketonuria. A phenylalanine-restricted diet, if started early and maintained
well, allows for normal development. However, if very strict control of the diet is not
maintained, affected children may begin to have difficulties in school. Dietary restrictions started
after 2 to 3 years of age may control extreme hyperactivity and seizures and raise the child’s
eventual intelligence quotient (IQ) but do not reverse intellectual disability. Recent evidence
suggests that some intellectually disabled adults with PKU (born before newborn screening tests
were available) may function better when they follow the PKU diet.

A phenylalanine-restricted diet should continue for life, or intelligence may decrease and
neurologic and mental problems may ensue.

Children who are born to mothers who have poorly controlled PKU (that is, they have high
phenylalanine levels) during pregnancy are at high risk of developing an abnormally small head
(microcephaly) and developmental problems. This condition is called maternal PKU.