Phenylketonuria (PKU)
PKU, or phenylketonuria (pronounced fen-il-Key-to-New-ree-uh), is a serious but manageable condition.
The incidence of PKU is about 1 in 15,000. Currently there is no cure for PKU. The only way to manage the
illness is through a lifelong strict diet. Understanding the nature of this condition is essential for managing a
child's condition. If left untreated PKU can cause problems with brain development, leading to mental
retardation and seizures.

PKU belongs to a class of diseases referred to as “inherited metabolic diseases,” or “inborn errors of
metabolism.” Metabolic diseases affect the body’s ability to execute certain chemical actions required for
normal growth and development. For people with PKU this means that a certain enzyme called phenylalanine
hydroxylase (PAH) is flawed. This enzyme is required for the breakdown of phenylalanine (Phe), an amino
acid found in foods containing protein. Even though they produce some working PAH, most of the PAH
they produce is faulty and doesn’t function the way it’s supposed to, and isn’t able to properly break the
Phe down.

PAH is a molecule produced in the liver, which sets in motion a chemical reaction that converts Phe into
another amino acid called tyrosine, or Tyr. For individuals who don’t have PKU, the liver produces enough
working PAH to convert Phe into Tyr, and as a result, all the Phe is utilized. For an individual with PKU, Phe
cannot be turned into Tyr and the excessive Phe builds up, passes into the bloodstream, and travels
throughout the body, eventually ending up in the brain. While a certain amount of Phe is essential for normal
growth and development, too much Phe in the brain causes damage, particularly in very young children.

Phenylketonuria (PKU) Diagnosis

PKU is normally detected using the HPLC test, but some clinics still use the Guthrie test, part of national
biochemical screening programs. Most babies in the U.S. are screened for PKU soon after birth. When a
child first tests positive for PKU, the results are sent to a lab at your local metabolic clinic to confirm a
diagnosis. The staff there is now committed to helping you and your child with the management of PKU,
including periodic blood testing, formula prescriptions, and dietary consultations based on feedback from
you and the blood tests. As part of managing your child’s condition, you will be required to stay in close
contact with the clinic.

Your child’s doctor will determine the frequency of Phe blood tests. In the beginning, your child may be
tested rather frequently while the clinic determines the appropriate diet. Testing can occur once or twice a
week until your child’s Phe levels become stable at an appropriate level. Once the levels are stable testing
may be required once a month until the child reaches adolescence. During adolescence through young
adulthood, testing may be conducted twice a year. In adulthood, yearly testing will likely continue for life.

Types of Phenylketonuria (PKU)

PKU is separated into two types: classic PKU and moderate PKU. These two types refer to different levels
of blood Phe. A person with moderate PKU has lower blood Phe levels than a person with classic PKU. Both
classic and moderate PKU patients can suffer significant neurological damage, if untreated, although this
damage is more significant in classic PKU.

The key to PKU management is keeping the amount of Phe in the blood within a safe range. To achieve the
proper blood Phe level, PKU management involves a three-step approach: Record, Restrict, and Replace. A
person with PKU (or the parent of a young child with PKU) must record the amount of Phe consumed;
restrict the diet to low-Phe foods; and replace those high-Phe foods with low-Phe alternatives most
commonly, a regimen of Phe-free medical protein supplement.

Causes for Phenylketonuria (PKU)

PKU is inherited. Both parents have to carry the PKU gene in order for a child to be born with PKU. You
don’t have to actually have PKU to carry the PKU gene. If you and your partner carry the gene but don’t
have PKU, there is a 25% chance that any future children you have together will have PKU. If one partner
has PKU, and the other is a carrier of the gene, the chance of having a child with PKU increases to 50%; if
both partners have PKU, the likelihood increases to 100.

Over 500 different genetic mutations have been identified that result in defective functioning of the
phenylalanine hydroxylase enzyme, resulting in elevated phenylalanine levels. Each different mutation or
combination of mutations results in more or less enzyme activity in the effected person.

Maternal Phenylketonuria (PKU)

For women affected with PKU, it is crucial for the health of their child to maintain low phenylalanine levels
before and during pregnancy. Though the developing fetus may only be a carrier of the PKU gene, the
intrauterine (location of the uterus) environment can have very high levels of phenylalanine, which can cross
the placenta. The result is that the child may develop congenital heart disease, growth retardation,
microcephaly (an abnormally small head and underdeveloped brain) and mental retardation. PKU affected
women themselves are not at risk from additional complications during pregnancy.

In most countries, women with PKU who wish to have children are advised to lower their blood
phenylalanine levels before they become pregnant and carefully control their phenylalanine levels throughout
the pregnancy. This is achieved by performing regular blood tests and adhering very strictly to a diet,
generally monitored on a day-to-day basis by a specialist metabolic dietitian. When low phenylalanine levels
are maintained for the duration of pregnancy there are no elevated levels of risk of birth defects compared
with a baby born to a non-PKU mother. Babies with PKU may drink breast milk, while also taking their
special metabolic formula. Some research has indicated that an exclusive diet of breast milk for PKU babies
may alter the effects of the deficiency, though during breastfeeding the mother must maintain a strict diet to
keep their phenylalanine levels low. More research is needed.

Phenylketonuria (PKU) Diet

The good news is that brain damage can be prevented. Currently, this is accomplished by restricting the
amount of Phe ingested. Foods that are very high in Phe, such as meat, eggs, dairy, and nuts are avoided
completely. These foods are replaced by a medical protein formula that has no Phe. Foods with moderate
amounts of Phe can be eaten but in limited quantities. These foods include certain fruits and starches. Most
foods have some Phe in them, meaning people with PKU must always be very careful about what they eat.
Therefore, it is important for individuals with PKU to track daily intake of Phe. With proper diet
management, newborns with PKU can look forward to healthy and fulfilling lives.

The PKU diet replaces meat, dairy, and eggs with a special medical formula that does not contain Phe. This
formula is prescribed by a doctor at a metabolic clinic. This formula is actually the centerpiece of the PKU
diet. For people with PKU, most of the calories they consume come from this formula, which may take the
form of a powder mixed with drinks or as a premixed drink. The remaining calories, and all of the Phe that a
person with PKU needs, come mostly from relatively low-Phe foods such as grains, fruits, and vegetables.
Since most food contains some Phe, people with PKU must be cautious about what—and how much—they
eat. Remember, it’s not that your child can’t consume protein, but rather your child can’t have too much of
a certain amino acid, Phe, that’s found in proteins. Individuals with PKU requiring dietary restriction may
never be taken off the special diet. This is often referred to as “diet for life.”

Phenylketonuria (PKU) Treatment

If PKU is diagnosed early enough, an affected newborn can grow up with normal brain development, but
only by eating a special diet low in phenylalanine for the rest of his or her life. This requires strictly
restricting or eliminating foods high in phenylalanine, such as breast milk, meat, chicken, fish, nuts, cheese,
legumes and other dairy products. Starchy foods such as potatoes, bread, pasta, and corn must be
monitored. Infants may still be breastfed to provide all of the benefits of breast milk, though the quantity
must be monitored and supplementation will be required. Many diet foods and diet soft drinks that contain
the sweetener aspartame must also be avoided, as aspartame consists of two amino acids: phenylalanine and
aspartic acid. A diet low in phenylalanine and high in tyrosine can be a very effective treatment.

Supplementary infant formulas are used in these patients to provide the amino acids and other necessary
nutrients that would otherwise be lacking in a protein free diet. These can continue in other forms as the
child grows up such as pills, formulas, and specially formulated foods. (Since phenylalanine is necessary for
the synthesis of many proteins, it is required but levels must be strictly controlled, usually being limited to 10
grams of protein. More severe forms of PKU, such as CPKU, require patients to be restricted to less than 5.
In addition, tyrosine, which is normally derived from phenylalanine, must be supplemented).

There are a number of other therapies currently under investigation, including gene therapy. There is at least
one specialized PKU treatment program in most US states. In some less-populated states, families may need
to travel to another nearby state, or the treatment may be coordinated through a state health department. All
children with PKU ideally should be followed by a specialized PKU program with adequate monitoring
facilities. Information about the nearest PKU treatment program can be obtained through the state newborn
screening program.
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