Phenylketonuria (fen-ul-ke-toe-NU-re-uh), also called PKU, is a rare inherited disorder that causes an amino acid called phenylalanine to build up in your body. PKU is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine.

Without the enzyme necessary to process phenylalanine, a dangerous buildup can develop when a person with PKU eats foods that are high in protein. This can eventually lead to serious health problems.

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.

Babies in the United States and many other countries are screened for PKU soon after birth. Recognizing PKU right away can help prevent major health problems.

Newborns with phenylketonuria initially don't have any symptoms. Without treatment, babies usually develop signs of PKU within a few months.

PKU symptoms can be mild or severe and may include:

  • Intellectual disability (formerly called mental retardation)
  • Delayed development
  • Behavioral, emotional and social problems
  • Psychiatric disorders
  • Neurological problems that may include seizures
  • Hyperactivity
  • Poor bone strength
  • Skin rashes (eczema)
  • A musty odor in the child's breath, skin or urine, caused by too much phenylalanine in the body
  • Fair skin and blue eyes, because phenylalanine cannot transform into melanin — the pigment responsible for hair and skin tone
  • Abnormally small head (microcephaly)

Severity varies

The most severe form of the disorder is called classic PKU. Children and adults with less severe forms of PKU, in which the faulty enzyme retains some function, have a smaller risk of significant brain damage. But most children with these forms of the disorder still require a special diet to prevent intellectual disability and other complications.

Pregnancy and PKU

A woman who has PKU and becomes pregnant is at risk of another form of the condition called maternal PKU. If a woman doesn'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. Even women with mild PKU may place their unborn children at risk by not following the PKU diet.

Babies born to mothers with high phenylalanine levels don't often inherit PKU. However, they can have serious consequences if the level of phenylalanine is high in the mother's blood. Complications at birth may include:

  • Intellectual disability
  • Low birth weight
  • Delayed development
  • Abnormally small head
  • Heart defects
  • Behavioral problems

When to see a doctor

Seek medical advice in these situations:

  • Newborns. If routine newborn screening tests show that your baby may have PKU, your child's doctor will want to start dietary treatment right away to prevent long-term problems.
  • Women of childbearing years. It's especially important for women with a history of PKU to see a doctor and maintain the PKU diet before becoming pregnant and during pregnancy to reduce the risk of high blood phenylalanine levels harming their unborn babies.
  • Adults. Adults with PKU continue to receive care across their life span. Older adults with PKU who may have stopped the PKU diet in their teens may benefit from a visit with their doctors. Returning to the diet may improve mental functioning and behavior and slow damage to the central nervous system in adults with high phenylalanine levels.

A genetic mutation causes phenylketonuria. In a person with PKU, this defective gene causes a lack of or deficiency of the enzyme that's needed to process an amino acid called phenylalanine. A dangerous buildup of phenylalanine can develop when a person with PKU eats foods that are high in protein, such as milk, cheese, nuts or meat.

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 have the defective gene, but not have the disease. This is called being a carrier. If only one parent has the PKU gene, there's no risk of passing PKU to a child, but it is possible for the child to be a carrier.

Most often, PKU is passed to children by two parents who are carriers of the disorder, but don't know it.

Risk factors for inheriting phenylketonuria include:

  • Having two parents with a defective PKU gene. Both parents must pass along a copy of the mutated PKU gene for their child to develop the condition.
  • Being of certain ethnic decent. The gene defect varies by ethnic groups and is less common in African-Americans than in other ethnic groups.

Children of mothers with PKU who didn't follow the PKU diet during pregnancy are at risk of birth defects due to the high levels of phenylalanine in their mothers' blood.

Untreated phenylketonuria can lead to:

  • Irreversible brain damage and marked intellectual disability within the first few months of life
  • Neurological problems such as seizures and tremors
  • Abnormally small head (microcephaly)
  • Behavioral, emotional and social problems in older children and adults
  • Significant health and developmental problems

Phenylketonuria is generally diagnosed through newborn screening. Once your child is diagnosed with PKU, you'll likely be referred to a medical center or specialty clinic with a doctor who specializes in treating PKU and a dietitian with expertise in the PKU diet.

Here's some information to help you get ready for your appointment.

What you can do

Before your appointment:

  • Ask a family member or friend to come with you — sometimes it can be difficult to remember all of the information provided during an appointment.
  • Make a list of questions to ask your doctor and dietitian to help you make the most of your time together.

For PKU, some basic questions to ask include:

  • How did my child get PKU?
  • How can we manage PKU?
  • Are there any medications to treat this disease?
  • What foods are completely off-limits?
  • What kind of formula will my child need?
  • What is the recommended diet?
  • Will my child have to stay on this special diet for life?
  • Are there any other supplements needed?
  • What happens if my child eats a food that he or she is not supposed to eat?
  • Is this condition temporary or long-lasting?
  • If I have another child, will he or she have PKU?
  • Are there brochures or other printed material that I can have? What websites do you recommend?

What to expect from your doctor

Your doctor is likely to ask you several questions. Be ready to answer them to reserve time to go over points you want to focus on. For example, your doctor may ask:

  • Has your child had any symptoms that concern you?
  • Do you have any questions about your child's diet?
  • Are you having any difficulty following the diet?
  • Has the growth and development of your child been normal?

Newborn blood testing identifies almost all cases of phenylketonuria. All 50 states in the United States require newborns to be screened for PKU. Many other countries also routinely screen infants for PKU.

If you have PKU or a family history of it, your doctor may recommend screening tests before pregnancy or birth. It's possible to identify PKU carriers through a blood test.

Testing your baby after birth

A PKU test is done a day or two after your baby's birth. The test isn't done before the baby is 24 hours old or before the baby has ingested some protein in the diet to ensure accurate results.

  • A nurse or lab technician collects a few drops of blood from your baby's heel or the bend in your baby's arm.
  • A laboratory tests the blood sample for certain metabolic disorders, including PKU.
  • If you don't deliver your baby in a hospital or are discharged soon after the birth, you may need to schedule a newborn screening with your pediatrician or family doctor.

If this test indicates your baby may have PKU:

  • Your baby may have additional tests to confirm the diagnosis, including more blood tests and urine tests
  • You and your baby may undergo genetic testing to identify gene mutations

The main treatment for phenylketonuria 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 you 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, the idea is to consume only the amount of phenylalanine that's necessary for normal growth and body processes, but no more. Your doctor can determine a safe amount through:

  • Regular review of diet records, growth charts and blood levels of phenylalanine
  • Frequent blood tests that monitor PKU levels as they change over time, especially during childhood growth spurts and pregnancy
  • Other tests that may be done to assess growth, development and health

Your doctor may refer you to a registered dietitian who can help you learn about the PKU diet.

Which 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

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 (NutraSweet, Equal). Aspartame, found in many artificial sweeteners, releases phenylalanine when digested.

Some medications may contain aspartame and some vitamins or other supplements may contain amino acids or skim milk powder. Check with your pharmacist about the contents of over-the-counter or prescription medications.

Talk with your doctor or dietitian to learn more about your specific dietary needs.

Formula for people with PKU

Because of the restricted diet, someone with PKU needs to get essential nutrition through a formula that's a special nutritional supplement for people with PKU. The phenylalanine-free formula provides protein and other essential nutrients in a form that's safe for people with PKU. Your doctor and dietitian can help you find the right type of formula.

  • 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 a sparing amount of breast milk or regular formula to be mixed with the phenylalanine-free formula. Parents introduce solid foods with low levels of phenylalanine to children with PKU on the same schedule used for other infants. These foods replace the phenylalanine a baby has been receiving from breast milk or formula and need to be precisely figured into the daily phenylalanine intake.
  • Formula for older children and adults. Older children and adults continue to drink or eat a protein substitute formula daily, as directed by a doctor or dietitian. Your daily dose of formula is divided between your meals and snacks, instead of consumed all at once. The formula for older children and adults is not the same as the one used for infants, but it works on the same principle. It acts as an essential nutritional substitute and is continued for life.

Another possible addition to the PKU diet is a supplement called neutral amino acid therapy in powder or tablet form. This supplement may block some absorption of phenylalanine. However, this is an emerging treatment that hasn't yet been well-studied. Ask your doctor or dietitian if this supplement is appropriate for your diet.

The need for a nutritional supplement, especially if your child doesn't find it palatable, and the limited food choices can make the PKU diet challenging. But families need to commit to this lifestyle change wholeheartedly because it's the only way to prevent the serious health problems that people with PKU can develop.

PKU medication

The Food and Drug Administration (FDA) has approved the drug sapropterin (Kuvan) for the treatment of PKU. It works by increasing your tolerance to phenylalanine. The drug is for use in combination with a PKU diet. But it doesn't work for everyone with PKU.

In approving sapropterin, the FDA directed that studies continue because there are no long-term studies on the drug's efficacy and long-term safety.

Keep track and measure correctly

If you or your child is following a low-phenylalanine diet, you'll need to keep records of the food eaten every day to be sure you're sticking to the specific, individualized dietary guidelines recommended by your dietitian.

To be as accurate as possible, measure the portions of your food using standard measuring cups and spoons and a kitchen scale that reads in grams. The food amounts are compared to a food list or are used to calculate the amount of phenylalanine eaten every day. Each meal and snack includes the appropriately divided portion of your daily PKU formula.

Food diaries or computer programs are available that list the amount of phenylalanine in baby foods, solid foods, PKU formulas, and common baking and cooking ingredients.

Buy low-protein products

Buying some of the many low-protein products, such as low-protein pasta, rice, flour and bread, which are available through specialty food retailers, may add variety to your diet.

These products allow people with PKU to eat lunches and dinners that more closely resemble what everyone else is eating. Like the PKU formulas, these products can be expensive, but you might consider splurging on a few favorites with the money you save on dairy and meat products.

Be creative

Talk with your dietitian to find out how you can be creative with foods, to help stay on track. For example, you can transform the same basic lower phenylalanine vegetables into a whole menu of different dishes, using a little creativity — and a lot of seasonings. Herbs and flavorings low in phenylalanine can pack a flavorful punch. Just remember to measure and count every ingredient and adjust ideas to your individualized diet.

If you have any other health conditions, you may need to consider those, too, when you plan your diet. Talk to your doctor or dietitian if you have any questions.

Living with phenylketonuria can be challenging. These strategies may help:

  • Stay informed. Knowing the facts about PKU can help you take charge of the situation. Discuss any questions with your pediatrician, family doctor or a doctor who specializes in medical genetics. Read books and cookbooks specifically written for people with PKU.
  • Learn from other families. Ask your doctor about local or online support groups for people dealing with PKU. Talking with others who have mastered similar challenges can be very helpful.
  • Get help with menu planning. A registered dietitian with experience in PKU can help you devise delicious low-phenylalanine dinners. He or she may also have great ideas for holiday meals and birthdays.
  • Plan ahead when you eat out. A meal at the local restaurant gives you a break from the kitchen and can be fun for the whole family. Most places offer something that fits into the PKU diet. But you may want to call ahead and ask about the menu or bring food from home.
  • Find sources of financial aid. Ask your doctor or dietitian if there are programs or insurance plans that help cover the high costs of formula and low-protein foods. Also, see if your local school lunch program will accommodate special dietary needs.
  • Don't focus on food. Encourage children with PKU to focus on sports, music or favorite hobbies, not on just what they can and can't eat. Also consider creating holiday traditions that center on special projects and activities, not just food.
  • Let your child manage his or her diet as early as possible. Toddlers can make choices about which cereal, fruit or vegetable they'd like to eat and help measure out portions. They can also help themselves to pre-measured snacks. Older children can help with menu planning, pack their own lunches and keep their own food records.
  • Make your grocery list and meals with the whole family in mind. A cupboard full of restricted foods can be tempting and irritating to a child or adult with PKU, so try to limit the number of forbidden foodstuffs. Also, try to avoid making separate meals that single out a child with PKU. Instead, make one meal for the whole family, even if the child with PKU can't eat everything. Serve stir-fried vegetables that are lower in protein. If the other family members wish, they can add peas, corn, meat and rice. Or set up a salad bar with low-protein and moderate-protein options. You can also serve the whole family a delicious low-phenylalanine soup or curry.
  • Be prepared for potlucks, picnics and car trips. Plan ahead, so there's always a PKU-friendly food option. Pack dehydrated fruit snacks, raisins and lower protein crackers for the car. Take fruit kebabs or vegetable skewers to a cookout, and make a low-phenylalanine salad for the neighborhood potluck. Other parents, friends and family members will likely be accommodating and helpful if you explain the dietary restrictions.
  • Talk to teachers and other staff in your child's school. Your child's teachers and cafeteria staff can be a big help with the PKU diet if you take the time to explain its importance and how it works. By working with your child's teachers, you can also plan ahead for special school events and parties so that your child always has a treat to eat.
  • Maintain a positive food attitude. When children know nothing but the foods they are given, they can be surprisingly accepting of the PKU diet — especially when their parents are positive problem-solvers.

If you're a woman with phenylketonuria who's considering having a baby:

  • 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. If you're a woman with PKU, talk to your doctor before you start trying to conceive.
  • Consider genetic counseling. If you have a history of PKU, a close relative with PKU or a child with PKU, you may also benefit from preconception genetic counseling. A doctor who specializes in medical genetics can help you better understand how PKU is passed through your family tree. He or she can also help you determine your risk of having a child with PKU and assist with family planning.
Nov. 26, 2014