Defects in Metabolism of Amino Acids: PKU

One condition that all newborns in the U.S. are screened for is phenylketonuria (PKU), a metabolic disorder passed down from both parents. Before the simple blood test that checks for PKU became routine, the condition could go undetected long enough to cause severe intellectual disability. Now the disorder can be diagnosed before it leads to any damage.

What is PKU?

PKU is caused by a defect in a gene known as the PAH gene. This defect changes the way that the amino acid phenylalanine is broken down by the body during digestion. Phenylalanine comes from commonly eaten foods. It helps the body make protein. It is also important for brain development. It is normally changed to tyrosine, which helps create all of the body's proteins. PKU affects 1 out of every 10,000 to 15,000 newborns norn in the U.S.

Because phenylalanine can't be properly processed when you have PKU, the amino acid can build up in the bloodstream and cause harm.

Causes of PKU

PKU is passed on to children when both parents have only 1 mutated gene. This means that neither parent has any symptoms of PKU but both are carriers of this gene. This gene mutation is recessive. This means that a person needs to inherit 1 gene from each parent in order to show signs of the disorder.

Feet of newborn baby

A baby born to a woman with PKU that is not well-controlled is at high risk for serious complications. In this case, the fetus can be exposed to extremely high levels of phenylalanine. This can cause low birth weight, slow growth, small head, behavior difficulties, and heart disorders. These mothers are also at risk for pregnancy loss.


In the U.S., all newborns are tested for PKU and placed on a special formula as soon as possible. It is unusual, therefore, for babies to develop symptoms of the disease. But if a baby isn't tested and has undiagnosed PKU, the child won't show any signs or symptoms until he or she is several months old. Sometimes babies with PKU may seem more drowsy and listless than normal, and they may have feeding difficulties. But as they continue to take in protein (and phenylalanine) through their diets, they may show other symptoms.

If PKU is not diagnosed and treated, phenylalanine will build up in the bloodstream until it reaches levels that are toxic to brain tissue. It can cause permanent damage to organs and tissues throughout the body.

PKU can lead to:

  • Developmental delays

  • Heart defects, especially in infants born to mothers with PKU and uncontrolled phenylalanine levels during pregnancy

  • Autism

  • Intellectual disability

  • Microcephaly, or very small head size

  • Behavioral problems

  • Seizures

  • Eczema, a skin condition marked by an itchy red rash or blisters

  • Pale hair and skin compared with that of other family members

  • Delayed physical growth

  • Low birth weight in babies

  • Musty body odor

Symptoms can range from mild to severe based on how high the levels of phenylalanine are in the blood.


Today, PKU rarely causes severe symptoms and damage in the U.S. because newborn screening and treatment is so widespread. Newborns are screened for PKU using a blood test. If you adopt children from another country, they may need to be screened for PKU, along with other genetic illnesses.


Children born with PKU will need to follow a special low-protein diet throughout their life. If they don't, they may suffer from mood disorders, poor memory and problem-solving skills, tremors, and depression.

Phenylalanine-free formulas are available for infants. As infants start to eat solid food, their diet will need to be restricted because phenylalanine is found in many typical protein-rich foods. For example, a child with PKU should not eat milk, fish, cheese, or meat. Foods low in protein, such as vegetables, fruits, and some cereals, can usually be eaten in certain quantities. Specific mineral and vitamin supplements may be needed to make up for missing nutrients in the diet.

Children and adults with PKU cannot tolerate the sugar substitute called aspartame and must read food labels to avoid sodas or any other products that contain it.


PKU can't be prevented, because the condition is inherited. Following the recommended low-protein diet can help prevent serious complications and permanent damage caused by PKU. Women with PKU who are of childbearing age should be particularly careful to follow a strict low-protein diet.