Phenylketonuria

Alternate Names
PKU
phenylalanine hydroxylase deficiency

Definition of Phenylketonuria

Phenylketonuria, abbreviated as PKU, is an inherited condition in which the body cannot process a substance in the diet, an amino acid called phenylalanine. PKU is an inborn error of metabolism that can lead to severe mental retardation if it is not treated.

What is going on in the body?

Phenylketonuria is caused by an enzyme defect in the liver. Normally, the liver produces an enzyme that breaks down phenylalanine, an amino acid found in many foods. The liver of a person with phenylketonuria does not produce this enzyme because of a genetic error. When this happens, phenylalanine and its by-products build up in the body, damaging brain tissue and leading to mental retardation.

What are the signs and symptoms of the disease?

A newborn who has PKU will appear normal. By the age of four months, symptoms of arrested brain development will begin to appear. If the PKU is untreated, severe, irreversible mental retardation will occur.

Signs and symptoms of PKU may include the following:

• abnormal movements, which may be writhing in nature
• behaviors resembling autism, which is a pervasive developmental delay
• decreased muscle tone
• difficulty walking
• a head that is smaller than normal in size
• learning disabilities
• a musty odor due to skin excretion of phenylacetic acid
• psychotic episodes, in which the person is unable to distinguish reality from fantasy
• rapid decrease in IQ in the first year of life
• seizures
• skin lesions or rough, dry skin

What are the causes and risks of the disease?

A problem in a gene causes the enzyme defect that leads to phenylketonuria. In order to have PKU, a person must inherit the abnormal gene from both parents. Phenylketonuria occurs in 1 of 15,000 live births. It is much more common in whites than in other racial groups.

What can be done to prevent the disease?

The genetic defect causing PKU cannot be prevented. If the defect is detected early in life, the child can be placed on a special diet low in phenylalanine, which he or she will need to follow carefully in order to prevent the mental retardation and learning disabilities.

How is the disease diagnosed?

Phenylketonuria is diagnosed when high levels of phenylalanine are found in the blood. Testing for PKU is generally done as a screening blood test on all infants within 48 hours of birth. Babies who test positive on the initial screening test will be evaluated again with a more specific test for PKU.

Phenylalanine levels may be normal at birth but go up once the baby is fed. It is important to evaluate babies after they have received dietary protein for 24 to 48 hours. The practice of discharging babies from the hospital within 24 hours of delivery has resulted in failure to detect some infants with PKU.

What are the long-term effects of the disease?

If treatment is started early in life, there are few long-term effects. Otherwise, affected persons may have serious learning disabilities. They may also die at a young age.

What are the risks to others?

Phenylketonuria is not contagious. However, a person with PKU will pass on an abnormal gene to his or her children. The children will not be affected, however, unless the other parent also has the abnormal gene. Parents who have a child with phenylketonuria are at risk for having other affected children. Genetic counseling can be helpful in this situation.

A woman with phenylketonuria must take special care during pregnancy. If she is on a regular diet, the enzyme defect may cause her unborn child to be severely affected. She will need to follow a special diet low in phenylalanine during pregnancy.

What are the treatments for the disease?

Treatment consists of limiting phenylalanine in the diet. Some healthcare professionals have been willing to relax the diet after several years of life.

However, in 2000, a consensus conference of the U.S. National Institutes of Health concluded that it was better for persons with PKU to observe dietary restrictions for life, since even in adulthood, some difficulties in mental function occur in those who stop observing the diet.

What are the side effects of the treatments?

There are no side effects to limiting phenylalanine in the diet. A person may find it challenging to avoid such foods. However, it is probably easier to stay on the diet lifelong than to try to get back on it once a person has become used to regular foods.

What happens after treatment for the disease?

Pregnant women with phenylketonuria need to avoid phenylalanine. Women with PKU who do not limit phenylalanine intake during pregnancy are at high risk of having a baby with defects, including the following:

• congenital heart disease
• low birth weight
• mental retardation
• small head size

How is the disease monitored?

Regular blood and urine tests will be done to monitor PKU. Any new or worsening symptoms should be reported to the healthcare professional.