Phenylketonuria (PKU) is a disorder in which a child lacks an enzyme necessary to process the essential amino acid known as phenylalanine. Essential amino acids can only be obtained from foods that are eaten since the body does not normally produce them. When levels of this amino acid (a building block of protein) become too high, it can cause brain damage that leads to progressive developmental delay and permanent mental retardation. About one in every 10,000 infants born in the United States has PKU, according to the National Institutes of Health.

PKU is the result of a defective recessive gene that is passed on from each parent to the child. If both parents are carriers of this gene, each of their children has a one in four chance of having PKU. Caucasians of northern European ancestry are at the highest risk for PKU. African-Americans and Asians are at much lower risk for PKU. Both male and females are equally affected.

Infants with PKU appear normal at birth. Symptoms commonly associated with untreated PKU include a distinctive musty or mousy odor on the child’s breath, skin, sweat and urine. Children with untreated PKU often have a lighter complexion than their siblings, because phenylalanine contributes to the production of melanin, which is the pigment responsible for hair and skin color. As children with untreated PKU get older they may have an abnormally small head (microcephaly), delayed mental and social skills, self-mutilation, stunted growth and seizures. 

PKU typically is diagnosed through blood tests.  A newborn screening test performed at the hospital after the baby’s birth is required in all states in the United States. If this screening test is positive, more specific tests are performed to diagnose the condition.

Children with PKU can live normal lives if they are treated early. The goal of treatment is to maintain blood levels of phenylalanine between 2 and 10 milligrams per deciliter (mg/dL). Treatment for PKU involves a special diet that is low in phenylalanine. This requires eliminating all high-protein foods, including meat, fish, milk, cheese, eggs, dried beans, peas and nuts. In addition, the artificial sweetener aspartame (commonly used in diet soft drinks) should be avoided because it contains phenylalanine. Children typically have to take a special liquid or supplement containing a nutritional substitute to help make up for the protein that is lacking in the diet. Phenylalanine levels in the blood should be checked regularly throughout childhood. PKU patients generally remain on restricted diets for life.

Phenylketonuria (PKU) is a rare metabolic disorder in which a child lacks an enzyme necessary to process an amino acid known as phenylalanine. This amino acid (a building block of protein) is essential for normal growth in infants and children and to help the body process protein. However, if the body allows too much phenylalanine to build up, brain damage can result.

About one in every 10,000 newborns in the United States has PKU, according to the National Institutes of Health. PKU rates vary throughout the rest of the world, depending on a child’s ethnic background and country of origin. In the United States, Caucasians of northern European ancestry are at the highest risk for PKU. African-Americans and Asians are at much lower risk for PKU. Worldwide, the highest incidence of PKU appears to occur in Turkey.

Unless treated, children with PKU usually will experience brain damage by the end of the first year of life. However, maintaining a strict low-protein diet can prevent or minimize the damage caused by PKU. Most experts recommend that the diet be continued throughout life. Going off the diet later in life has been associated with a drop in cognitive function and other complications, such as movement disorders and attention-deficit hyperactivity disorder.

Phenylketonuria (PKU) is the result of a defective gene that is passed on from each parent to the child. This is known as an autosomal recessive trait. Parents sometimes have PKU themselves, but more often they are carriers of the gene. This means they have the defective gene, but do not have PKU itself. Parents who are considering having a child can have genetic testing to see if they are carriers for PKU. When both parents carry the defective gene, they have a one in four chance that each child will have PKU.

Children who inherit this genetic deficiency from each parent are missing or are deficient in an enzyme called phenylalanine hydroxylase. This enzyme processes the amino acid phenylalanine in the body. If only one parent passes on the defective gene, the child will not have PKU.

This absence or deficiency of phenylalanine hydroxylase causes levels of phenylalanine and two other phenylalanine derivatives to build up in the body. High levels of these substances in tissues and the bloodstream are toxic to the central nervous system, which can result in brain damage and other neurological symptoms.

Phenylketonuria (PKU) that is not treated causes several characteristic symptoms that range from mild to severe and differ from child to child. Children with PKU often have a lighter complexion (including blond hair and blue eyes) than their siblings, because phenylalanine contributes to the production of melanin, which is the pigment responsible for hair and skin color. As the derivative phenylacetic acid builds up, it may cause a musty or mousy odor on the child’s breath, skin, sweat and urine. These are the first noticeable symptoms.

Typically, children with PKU appear to behave normally until they are a few months old. At this point, symptoms first appear, and may include loss of interest in their surroundings. By the time a child is one year old, developmental delays typically are obvious.

Older children with untreated PKU may develop other symptoms. These include attention-deficit hyperactivity disorder (ADHD), seizures, movement disorders (athetosis) and rocking.

 Other symptoms associated with PKU include:

• Abnormally small head (microcephaly)
• Delayed mental and social skills
• Heart defects
• Jerking movements of the arms or legs (spasticity)
• Mental retardation
• Skin rashes (e.g., eczema)
• Stunted growth
• Tremors
• Unusual hand posturing
• Vomiting

Phenylketonuria (PKU) typically is diagnosed through a blood test. A newborn screening test is performed at the hospital after the baby’s birth. All 50 states require this testing, which is usually performed with a heelstick (prick in the heel) a day or two after the baby is born. Performing the test in the first 24 hours after birth may result in inaccuracies (false negatives). In addition, the test must not be performed until the child has ingested some protein. Tests are considered highly accurate as long as they are performed within seven days of birth. If the screening test is positive, further testing will be performed to positively diagnose PKU. Researchers are investigating potential new blood tests to detect PKU, including improving the accuracy of earlier tests.

In some cases, chorionic villus sampling (CVS) may be performed prior to a child’s birth to detect PKU. During this procedure, a needle is inserted into the lower belly of a pregnant woman to obtain a small sampling of cells from the placenta for analysis. 

If children are diagnosed with PKU, they will undergo treatment that involves a special diet to prevent possible brain damage. Older adults who have a history of PKU, have gone off the diet and have experienced deficits in motor function and cognitive difficulties or decline may undergo magnetic resonance imaging (MRI) testing to determine if the condition has affected the brain. MRI testing can reveal evidence of demyelination (loss of myelin, a substance in the white matter that insulates nerve endings).

Children with phenylketonuria (PKU) can live normal lives if they receive early treatment. It is estimated that children who are well treated will have intelligence quotient (IQ) levels that are within five to eight points of their siblings. Children who are left untreated – or who are not treated until after the age of three – will inevitably experience brain damage. However, very mild cases of PKU may not require treatment. 

The chief treatment for PKU is a special diet that is low in phenylalanine and contains just enough of this amino acid to promote normal growth and body processes. This begins in infancy, with a special formula that is low in this amino acid. Babies who are breastfed may consume a combination of special formula and some breastmilk. Blood levels of phenylalanine will be monitored throughout life. The goal of treatment is to maintain blood levels of phenylalanine between 2 and 10 milligrams per deciliter (mg/dL). The frequency of testing may vary by child, ranging from weekly to monthly.

As the children begin to eat solid foods, their diet will be restricted so that all high-protein foods are eliminated. Such foods include meat, milk, cheese, eggs and nuts. Children typically have to take a special liquid or supplement containing a nutritional substitute to help make up for the protein that is lacking in the diet.

Parents work with a physician and dietitian to create a proper diet for children with PKU. Children will have to remain on this diet through adolescence, and usually for the rest of their lives. Children who follow this diet closely can lead normal lives. Previously, it was believed that diets could be ended around age six, when brain growth was completed. However, more recent study has revealed that high blood levels of phenylalanine may lead to a decrease in a child's IQ (intelligence quotient) or to other developmental and behavioral problems.

It is important that children and others with PKU avoid consuming aspartame. This artificial sweetener contains phenylalanine and is found in many sweets, diet soft drinks and medications. Children with PKU will also have to consume limited amounts of certain other foods that contain phenylalanine, including pasta, rice, bread, cookies and some fruits and vegetables.

Many children and parents find it challenging to adhere to the strict diet necessary to prevent damage associated with PKU. Food diaries and computer programs are available to help parents and children to plan and create meals that are safe. In addition, specialty foods and ingredients are available that are low in phenylalanine. These allow children with PKU to indulge in favorites such as pizza, cookies and pasta.

Once a special diet has been established, patients will continue to undergo follow-up monitoring to ensure that their blood phenylalanine levels are in the proper range. Blood tests can determine whether or not these levels are too high or too low. Testing of babies may take place weekly, while testing is likely to be once or twice a month during childhood.

People who are considering having children may want to undergo genetic testing to see if they are carriers of the gene that results in phenylketonuria (PKU). In addition, the March of Dimes recommends that all women who were treated for PKU as a child have their blood phenylalanine levels checked prior to becoming pregnant. This can help a physician determine whether or not these women need to go on a special low-phenylalanine diet prior to conception. This type of diet can lower the woman’s risk of miscarriage or brain damage, congenital heart disease or microcephaly in the fetus.

Women should control phenylalanine levels both before and during pregnancy. Even mild levels of PKU in pregnant women present potential danger to the fetus. For this reason, women who were not treated for PKU as children still should have their blood phenylalanine levels checked if they have a family history of PKU.

Most experts recommend that patients with PKU should remain on a special diet throughout their lifetime. Previously, it was believed that diets could be ended around age six, when brain growth was completed. However, more recent study has revealed that high blood levels of phenylalanine may lead to a decrease in a child’s IQ (intelligence quotient) or to other developmental and behavioral problems

Preparing questions in advance can help patients and parents to have more meaningful discussions with their physicians regarding their or their child’s treatment options. The following questions related to phenylketonuria (PKU) may be helpful:

1. Should my partner and I undergo genetic testing before having children?
   
   
2. If we test positive, should we refrain from having children?
   
   
3. I am a carrier of PKU. How can I reduce the risk of passing PKU onto my child?
   
   
4. Do you suggest having chorionic villus sampling performed on my fetus?
   
   
5. When will my child be tested for PKU?
   
   
6. If my child tests positive, what are our treatment options?
   
   
7. Where can I find a formula that is low in phenylalanine?
   
   
8. Will I need to work with a dietician to plan a safe diet for my child?
   
   
9. What other resources can help me plan safe meals?
   
   
10. What are the odds that our future children will have PKU?
    
    
11. What should I tell my child’s school about diet restrictions?
    
    
12. What happens if my child eats a lot of protein by mistake?