The PKU (Phenylketonuria) Test

What is PKU?

Phenylketonuria is also known more commonly as PKU. It is an inherited disorder characterized by increases of phenylalanine (Phe) in a person’s blood.

PKU is also known by other names as well, including:

1.  deficiency disease
2.  phenylalanine hydroxylase
3.  Folling disease or Folling's disease
4.  PAH deficiency
5.  Phenylalanine Hydroxylase Deficiency

Phenylalanine is an amino acid that is a building block of proteins found in all proteins and in some artificial sweeteners. It is absorbed into the body through a person’s diet.

If it is not treated, PKU can build up in the body causing harm in the form of intellectual disabilities and other serious health problems.

Signs and Symptoms of PKU

Cases of PKU can range from mild to severe. The most severe form of PKU is known as classic PKU.

Infants can appear normal until they are a few months old, but without treatment, they can develop permanent intellectual disabilities that can be characterized by seizures, behavioral problems, psychiatric disorders and delayed development.

Children with classic PKU will have lighter skin and hair than other family members. They are also more likely to have eczema and other skin disorders.

Babies born to mothers who have PKU and who no longer follow a low-phenylalanine diet have a major risk of intellectual disability because they are exposed to very high levels of Phe before birth. These infants also have a low birth weight and will grow slower than other children.

Other medical problems associated with PKU include heart defects, an abnormally small head size, and behavioral problems. Women with PKU and uncontrolled Phe levels also have an increased risk of pregnancy loss.

Excess Phe also produces a musty or mouse-like odor when left untreated.

Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia and milder forms of this condition and carry a small risk of brain damage.

The prevalence of PKU varies widely in ethnic groups and geographic regions throughout the world. In the United States, PKU take place in 1 in 10,000 to 15,000 newborns ¹.

In the United States, PKU is most common in people who are of European or Native American descent ². It is much less common in people of African, Hispanic, or Asian ancestry.

The good news is that most cases of PKU are detected shortly after birth and treatment is started promptly. Because of this, severe cases of classic PKU are rare.

What causes PKU?

PKU is caused by mutations in the gene that helps make an enzyme called phenylalanine hydroxylase. This enzyme is also known as PAH.

PAH is needed to convert the amino acid phenylalanine into other substances that a body needs. When the PAH gene has mutated and is no longer able to do its job, the body is not able to break down phenylalanine.

When these gene mutations reduce the activity of phenylalanine hydroxylase, that means phenylalanine from the diet is not processed effectively. The body is unable to break it down.

This amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.

Although some PAH mutations can cause PKU, other mutations in the PAH gene that allow the enzyme to retain some activity result in milder versions of this condition.

These milder conditions are known as variant PKU or non-PKU hyperphenylalaninemia. In some cases, the mutations are silent are silent and do not have an effect.

PKU is Inherited

PKU is an inherited disorder passed down from generation to generation in an autosomal recessive pattern. This means that for a child to develop PKU, both parents must pass down and contribute a mutated version of the PAH gene. If both parents have PKU, then their children will have PKU as well.

The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

However, if both parents carry the mutated PAH gene, their children may still not develop PKU. This is because a child's parents each carry two versions of the PAH gene, only one of which they will pass on during conception.

If only one parent carries the mutated PAH gene, the child will not develop PKU.

There are times when a parent is only a carrier of the mutated PAH gene but does not have PKU.

If both of a child's parents are carriers, there is a 25% chance that each parent will pass on the normal PAH gene.

But there is also a 25% chance that the carrier parents will both pass along the mutated gene, causing the child to have PKU.

There is a 50% chance that a child will inherit one normal gene from one parent and one abnormal one from the other, making the child a carrier.

About 1 out of every 50 Caucasians is a PKU carrier.

Some genetic disorders, including PKU, develop more often among people whose ancestors come from a particular region. It’s not uncommon that shared versions of their genes have been passed down from common ancestors. This includes mutated genes that can cause PKU.

What is a PKU Test?

Every infant in the United States is tested for PKU. It is part of newborn screenings that check for a number of conditions. The PKU test measures the amount of Phe in your baby’s blood.

A blood sample will be drawn from your newborn no earlier than 24 hours after the baby is born.

Blood is usually taken through a prick on the newborn’s heel. It’s put on a special paper and sent to a lab for analysis. When the results come back, your baby’s doctor will share the results with you.

If the PKU test comes back positive, you need to understand that there is no cure. However, identifying PKU will result in getting treatment so that your baby can grow into a healthy adult.

A normal Phe level is less than 2 milligrams per deciliter. More than 4 mg/dL is considered high. Even if a baby’s results aren’t in that range, it doesn’t necessarily mean he or she has PKU. It means more tests are needed to find out for sure.

PKU tests on premature babies could produce a “false positive” because the enzyme to break down Phe hasn’t developed fully yet.

A “false negative” is also possible if the baby isn’t eating (either breastfed or bottle-fed), is throwing up, or if a PKU test was done too soon after birth.

The only risk in having the test administered is a small bruise may develop where the heel stick took place.

How is PKU Treated?

Children with PKU needs to be on a special, lifelong diet that’s low in Phe. The optimal way to treat the condition is to put the newborn on a Phe-free infant formula within 7-10 days after being born. Some breast milk may also be allowable.

Children who start treatment after 6 months of age often develop intellectual disabilities. Treatment is still important at any age, because it helps control behavior and mood problems while also preventing more damage to the brain.

As they grow, some children need a stricter diet than others. A dietitian with expertise in PKU can make an eating plan specific to your child so he or she grows and thrives.

This may mean carefully measured portions of fruits, vegetables, and low-protein cereals, bread, and pasta.

Foods with higher levels of Phe generally are off-limits. These include ³:

1. Milk and Dairy products like cheese, yogurt and ice cream
2. Eggs
3.  Meat, poultry, and fish
4.  Nuts and peanut butter
5.  Beans
6. Foods or drinks with the artificial sweetener aspartame typically sold under the brand names “Equal”, "Nutrasweet” “Sweetmate”, “Canderal”

When a child’s diet is limited, he or she will need to drink a special formula that contains protein (minus the Phe) and all the other nutrients that are needed.

Lots of vegetables and fruits have small amounts of Phe and can be eaten in small measured amounts.

A food plan will depend on several things such as age, weight, general health, and blood test results. Your dietician will fine-tune your child’s diet over time.

Blood tests and doctor visits on a regular basis will help to show whether the diet is working.

Adults with uncontrolled high concentrations of PKU can be treated the medication pegvaliase-pqpz (Palynziq) to help reduce levels.

Others take a prescription such as sapopterin (Kuvan) that helps process Phe. It’s more likely to work in those with mild or special forms of PKU.

Children will continue with their special diets but may have more freedom to deviate while taking the medication.

Some children with PKU will benefit from taking BH4 supplements, especially those with mild PKU.

Is genetic testing for PKU Available?

Genetic testing for PKU can be done with a blood sample. The test will look for changes in the pair of genes that causes PKU.

DNA testing is not necessary to diagnose a child but is sometimes helpful to know what the gene changes are in a child with PKU because it may help the doctors and dietician develop the best treatment plan.

If gene changes have been found in one child, other family members can have DNA testing to see if they are also PKU carriers. If DNA testing is not helpful, other methods of carrier testing may be available.

If you have questions about carrier testing, seek out a genetic counselor or metabolic doctor.

When can PKU Testing be Done?

A PKU test can be done as soon as 24 hours after a baby has been born. It’s important to have this test as soon as possible so that if a baby has PKU (or other birth disorders), treatment can start immediately.

This means larger related health problems, such a brain damage, are less likely to take place.

There are no preparations necessary before a baby has a test. Tests are ordered by your health care provider and can be done at any hospital or laboratory.

You can also choose prenatal screening that will cover a broad spectrum of possibly having a baby with birth defects, including PKU.

Testing for PKU During Pregnancy

If gene mutations have been found in one of your existing children with PKU, then genetic testing can be done during future pregnancies. This will help a family prepare for the possibility that a child in utero may be born with PKU as well.

The sample to conduct this test can be obtained either by amniocentesis or by Chorionic Villus Sampling (CVS). Testing is usually done early on, at about 10 to 12 weeks of pregnancy.

The other option is to wait until birth to have the newborn tested. It may be best to consult with a genetic counselor to talk about your options and get answers to prenatal testing vs. testing a baby after birth.

Understanding Your Baby’s PKU Test Results

Results for PKU tests usually take about two to three weeks. If results from one of the tests comes back positive, it means that one of the tests came back outside the normal range.

Some doctors may also characterize this result as failing, abnormal or out-of-range.

A positive result does not automatically mean that a baby has PKU. What is means is that more testing is warranted and should be performed as soon as possible ⁴.

Follow-up testing will involve checking the baby’s urine and blood samples for harmful levels of acids and toxins. If a baby does have PKU, then a treatment plan can be put in place immediately to minimize the impacts of the disorder.

There are instances when follow-up diagnostic testing shows that the baby does not have PKU. When this happens, it means that the initial test produced a “false positive” result.

False positive test results can happen because screening tests are designed to identify as many babies affected with treatable diseases as possible. It is more important initially to make sure that a screening does not miss any affected babies, so some babies who are unaffected may also end up with a positive result.

In some other cases, test results may be inconclusive or labeled as a “borderline” result. When this happens, a doctor may repeat the test to get a more accurate result.

If a baby’s results show certain signs of PKU, a doctor may recommend starting immediate treatment that may include the doctor and a dietician monitoring a baby’s protein intake to ensure that their blood Phe level is stabilized. Keeping it at an optimal level ensures appropriate growth and development.

Mothers should still be able to breastfeed their babies. A dietician will work with the mother to create a breastfeeding plan that can be supplemented with medical formula.

It may take a few months to get this dialed in and have the baby adjust to their life. Phe levels can fluctuate, especially when a child gets sick, so there are certain protocols that must be followed in those instances as well ⁵.

While Phe levels that fluctuate can produce anxiety in parents, it’s important to note that damage from PKU only takes place when babies go off their treatment for extended periods of time.

As a baby grows into a child and becomes older, PKU will become a small part of who they are and how they will need to take care of themselves.

The upside of this is that children with PKU must learn to take responsibility for their diets early in their lives and this translates into developing other life skills such as self-discipline, responsibility and accountability that helps them to become successful in life.

PKU Support Groups

Because PKU is a lifelong condition, finding help and support is a wise move to help affected connect families. Supportive people will be able to steer parents to resources and people who have experience living with the condition.

Some of the more well-known support and resource groups include:

• National PKU Alliance (NPKUA)
  The NPKUA is the first national nonprofit that brings together adults, families, statewide organizations, the medical community, and PKU-friendly businesses under a single organization.

• PKU Toolkit by the Boston Children’s Hospital
  This toolkit is a guide for managing PKU. It includes information on PKU and the low-Phe diet, insurance, life transitions, lifestyle, maternal PKU and other related subjects.

• The National Organization for Rare Disorders (NORD)
  NORD helps eligible patients with medical and financial needs to be able to afford the medications and treatments their healthcare professionals have prescribed.

• Children’s PKU Network (CPN)
  CPN is a nonprofit that aids individuals and families with PKU through public awareness, education, and direct assistance to help those diagnosed with PKU to reach their full potential.

• National PKU News

There are also a number of regional PKU organizations to help you find support closer to home:

• Canadian PKU and Allied Disorders
• California Coalition for PKU and Allied Disorders
• Georgia PKU Connection
• PKU Organization of Illinois
• Indiana PKU and Allied Disorders Association
• Maryland Alliance of PKU Families, Inc.
• Michigan PKU & Associated Disorders, Inc.
• New England Connection for PKU and Allied Disorders
• Tennessee PKU Foundation
• Michigan Department of Health and Human Services
• Texas Department of State Health Services

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