Phenylketonuria (PKU)

Topic Overview

What is phenylketonuria (PKU)?

Phenylketonuria (PKU) is a genetic disorder in which a baby lacks or has very low levels of the enzyme phenylalanine hydroxylase (PAH). This enzyme is necessary to convert phenylalanine, an amino acid, into another amino acid called tyrosine after protein is eaten. If PKU is not treated soon after birth, phenylalanine builds up in the bloodstream and brain tissue, causing mental retardation and central nervous system problems. If PKU is treated soon after birth, all or most of these problems can usually be prevented.

Each year, about 250 U.S. children get PKU.¹ It is more common in whites and Native Americans than in blacks, Hispanics, and Asians.²

What causes PKU?

PKU is an autosomal recessive disease. This means that to have the disease, you must inherit the gene from each parent. If you inherit the gene from only one parent, you are a carrier of PKU but do not have the disease.

What are the symptoms?

Symptoms usually develop within a few months after birth, when phenylalanine has built up in a baby's system from consuming the protein in formula or breast milk. Before birth, the mother's body filters out the excess phenylalanine for the baby (fetus).

Early symptoms of PKU include a musty odor to the skin, hair, and urine. Babies may lose weight from vomiting and frequent diarrhea, and may be irritable, have skin problems, and be sensitive to light.

If phenylalanine levels increase, an older child may develop unusual behavior, such as screaming episodes, repetitive rocking, head banging, and arm biting. The child may also have growth and developmental delays, frequent seizures, and, if not treated, will become severely mentally retarded.

How is PKU diagnosed?

All babies born in the United States are tested for PKU within a few days after birth. Phenylalanine levels are measured in a blood sample taken from the baby's heel. The test may be repeated within the first week or two after birth.

If you have a family history of phenylketonuria, talk with your health professional about genetic testing. If you have a child with PKU, it may be helpful to get genetic counseling if you are considering having another child.

How is it treated?

The main treatment for PKU is a lifelong, special reduced-protein diet. This helps prevent phenylalanine from building up in the body. But because phenylalanine is needed for normal growth and development, it cannot be completely eliminated from the diet. Early diagnosis and treatment usually prevent injury to the baby's brain and other long-term problems.

Women of childbearing age who have PKU must carefully control their phenylalanine levels. Babies born to mothers who have high phenylalanine levels during pregnancy are at risk for mental retardation, having an unusually small head (microcephaly), physical growth problems, and congenital heart disease.

Frequently Asked Questions

Symptoms

Symptoms of phenylketonuria (PKU) usually develop within a few months after birth, after phenylalanine has built up in a baby's system from consuming the protein in formula or breast milk. Before birth, the mother's body filters out the excess phenylalanine for the baby (fetus).

Early symptoms of PKU, which occur in more than half of babies with this condition, include:³

• A musty odor to the skin, hair, and urine.
• Vomiting and diarrhea, leading to weight loss.
• Irritability.
• Skin problems, such as dry skin, or itchy skin rashes (eczema).
• Sensitivity to light (photosensitivity).

If a baby has especially low levels of the enzyme needed to prevent phenylalanine build-up or if PKU is not detected and treated soon enough, phenylalanine builds up in the brain tissue. It then affects mental skills and the central nervous system. Symptoms can become severe by about 8 weeks of age and may include:

• Unusual behavior, such as screaming episodes, repetitive rocking, head banging, and arm biting (common in older children).
• Loss of skills and abilities related to severe mental retardation.
• Growth and developmental delays.
• Seizures.

PKU also affects the synthesis of melanin, which provides pigment (color) to the skin, eyes, and hair. About 90% of children with PKU have blond hair, fair skin, and blue eyes.³

Exams and Tests

Within a few days of birth, all babies in the United States are tested for phenylketonuria (PKU). The test for phenylketonuria uses two or three drops of blood taken from your baby's heel to measure phenylalanine levels. Phenylalanine blood levels are higher in babies with PKU.

Most doctors will take the blood sample after your baby has been fed, 24 to 48 hours after birth.² It can take a few days for phenylalanine to build up in a newborn's body, so testing before 24 hours can give untrue results (false negatives).

Periodic blood tests to measure phenylalanine levels are recommended for babies and pregnant women with PKU. Babies may get tested as often as once a week for the first year and then once or twice a month throughout childhood. Pregnant women with PKU should be tested at least once a week.

PKU is an autosomal recessive disease, which means it will only develop if a person inherits the gene from both parents. If the PKU gene is inherited from only one parent, the person will be a carrier of the gene for PKU but will not develop the disease. The risk of passing on an autosomal recessive disease depends on your family medical history. Ask your doctor about a genetic test if you are interested in confirming whether you carry the gene for PKU.

Treatment Overview

The main treatment for phenylketonuria (PKU) consists of permanently reducing the amount of protein in the diet. For a few people, medicine may help reduce phenylalanine blood levels when used with a PKU diet.

Protein contains phenylalanine, an amino acid that is essential for normal growth and development. People with PKU lack an enzyme to properly metabolize phenylalanine. Very high levels of phenylalanine in the blood can lead to irreversible brain and nervous system damage.

Experts recommend feeding your newborn a phenylalanine-free formula within 7 to 10 days after birth.⁴ You may also be able to feed your baby breast milk, but talk to your baby's doctor first. During your baby's first year, blood tests to measure phenylalanine levels are usually done weekly.

Although any brain or nervous system damage that develops is irreversible, problems are less likely to occur if a PKU diet starts by 3 weeks of age. Your baby will most likely grow and develop normally when feedings with low-phenylalanine formula are used. In rare cases, children may have learning or behavior problems (such as slower language development, hyperactivity, anxiety, and poor concentration) despite early treatment.

A reduced-protein diet should be consistently followed throughout life. As your child grows, the diet is individualized and adjusted according to his or her specific needs. Hunger levels, growth, development, behavior, illness, food preferences, and phenylalanine blood levels are all taken into consideration.

A few people may be able to take the medicine sapropterin dihydrochloride (Kuvan) to help lower phenylalanine levels. A PKU diet needs to be followed while this medicine is taken. It's not known if Kuvan helps reduce long-term nervous system problems. And its safety has not been studied in children younger than age 4 or in adults age 65 and older. Talk to your doctor if you want to know if it's safe for you or your child.

It is important to have regular blood tests to measure phenylalanine levels. From ages 1 to 12, testing is usually done twice a month. After age 12 and throughout adulthood, testing once a month is suggested. High levels of phenylalanine in teens and adults negatively affect IQ (intelligent quotient) and cognitive functions such as awareness, knowledge, thinking, learning, and judgment.

Maternal PKU

The American Academy of Pediatrics and other expert groups offer recommendations and guidelines for preventing and managing PKU in women who are or who may become pregnant. Generally, women who have PKU and want to have a baby need to follow the PKU diet and get enough nutrients to support a growing fetus.

It is best to adopt the PKU diet before becoming pregnant. Mental retardation can occur in as many as half of the children who have mothers with uncontrolled PKU during most of their pregnancy.^{5, 6} High levels of phenylalanine in the mother during pregnancy can also cause babies to be born with abnormally small heads (microcephaly), growth problems, and congenital heart disease.

Women with PKU who are considering becoming pregnant should also have periodic blood tests, as advised by their health professional, to measure phenylalanine levels. Low levels (below 6 mg/dL) of phenylalanine should be reached at least 3 months before conception. Recommended levels are 2 mg/dL to 6 mg/dL.⁷ After a woman is pregnant, she should be tested at least once a week until the baby is born.

Home Treatment

Home treatment for phenylketonuria (PKU) focuses on managing phenylalanine levels throughout life.

Follow the dietary guidelines Learn about the disorder and explain its effects to your child. Stress the importance of staying on the PKU diet, and involve your child in selecting appropriate foods. It is a good idea to seek suggestions from a registered dietitian for ideas about types of foods, recipes, and how to ensure your child's nutritional needs are being met. Adults with PKU will also benefit from this information. Be aware that foods low in phenylalanine often cost more.

Work with your health professional Set up a schedule for checking blood phenylalanine levels. Periodic testing is needed throughout life. The frequency depends on your age and severity of enzyme deficiency. It's also important for children who have PKU to get regular dental care, because amino acid supplements can sometimes wear down the teeth.

Manage maternal PKU If you are a woman with PKU who is considering pregnancy, follow the American Academy of Pediatrics (AAP) recommendations. High levels of phenylalanine in the mother could cause the baby to be born mentally retarded or with other health problems, such as an unusually small head (microcephaly). Following the PKU diet both before and during pregnancy will help keep your baby (fetus) healthy. Women with PKU should be tested for PKU levels twice a week during pregnancy.

Seek genetic testing If you have a family history of PKU, talk with your doctor about a genetic test. If you have a child with PKU, it may be helpful to seek genetic counseling before attempting another pregnancy.

Join a support group If you or your child has PKU, you may want to join a support group or talk with families who are dealing with similar issues. Remember that it is normal to have feelings of anger, depression, guilt, and frustration when living with PKU or when caring for someone else with the condition. Don't be afraid to talk with your health professional about such feelings. It may also be helpful to encourage your child to participate in a support group in which he or she can express personal feelings.

Other Places To Get Help

Organizations

Related Information

• Early Disease Detection
• Genetics
• Growth and Development, Newborn
• Phenylketonuria (PKU) Test

References

Citations

1. National Institutes of Health (2006). Fact sheet: Mental retardation. Available online: http://www.nih.gov/about/researchresultsforthepublic/MentalRetardation.pdf.

2. Rezvani I (2007). Phenylalanine section of Defects in metabolism of amino acids. In RM Kliegman et al., eds., Nelson Textbook of Pediatrics, 18th ed., chap. 85, pp. 529-532. Philadelphia: Saunders Elsevier.

3. Grompe M (2003). Phenylketonuria section of Disorders of acid metabolism. In CD Rudolph, AM Rudolph, eds., Rudolph's Pediatrics, 21st ed., chap. 9.2, pp. 609-611. New York: McGraw-Hill.

4. March of Dimes (2007). PKU (Phenylketonuria). Available online: http://www.marchofdimes.com/pnhec/4439_1219.asp.

5. Waisbren SE, Azen C (2003). Cognitive and behavioral development in maternal phenylketonuria offspring. Pediatrics, 112(6 Part 2): 1544-1547.

6. Wappner RS (2006). Disorders of phenylalanine and tyrosine metabolism section of Disorders of amino acid and organic acid metabolism. In JA McMillan et al., eds., Oski's Pediatrics: Principles and Practice, 4th ed., chap. 385, pp. 2153-2157. Philadelphia: Lippincott Williams and Wilkins.

7. Kaye CI, and the Committee on Genetics, American Academy of Pediatrics (2006). Phenylketonuria section of Newborn screening fact sheets: Technical report. Pediatrics, 118(3): e956-e957.

Other Works Consulted

• Accardo PJ, et al. (2006). Mental retardation. In JA McMillan et al., eds., Oski's Pediatrics: Principles and Practice, 4th ed., chap. 98, pp. 608-614. Philadelphia: Lippincott Williams and Wilkins.

• Durkin MS, et al. (2008). Childhood cognitive disability. In RB Wallace et al., eds., Wallace/Maxcy-Rosenau-Last Public Health and Preventive Medicine, 15th ed., pp. 1173-1183. New York: McGraw-Hill.

• National Institutes of Health (2000). Phenylketonuria (PKU): Screening and management. NIH Consensus Statement, 17(3): 1-33.

• Ropper AH , Brown RH (2005). The inherited metabolic diseases of the nervous system. In Adams and Victor's Principles of Neurology, 8th ed., pp. 797-849. New York: McGraw-Hill.

• Thomas JA, Van Hove JLK (2007). Phenylketonuria and the hyperphenylalaninemias section of Inborn errors of metabolism. In WW Hay Jr et al., eds., Current Pediatric Diagnosis and Treatment, 18th ed., pp. 996-997. New York: McGraw-Hill.

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