Phenylketonuria (PKU) is an inherited disorder of metabolism that causes an increase in the blood of a chemical known as phenylalanine. Phenylalanine comes from a person's diet and is used by the body to make proteins. Phenylalanine is found in all food proteins and in some artificial sweeteners. Without dietary treatment, phenylalanine can build up to harmful levels in the body, causing mental retardation and other serious problems.
Women who have high levels of phenylalanine during pregnancy are at high risk for having babies born with mental retardation, heart problems, small head size (microcephaly) and developmental delay. This is because the babies are exposed to their mother's very high levels of phenylalanine before they are born.
In the United States, PKU occurs in 1 in 10,000 to 1 in 15,000 newborn babies. Newborn screening has been used to detect PKU since the 1960's. As a result, the severe signs and symptoms of PKU are rarely seen.
Symptoms of PKU range from mild to severe. Severe PKU is called classic PKU. Infants born with classic PKU appear normal for the first few months after birth. However, without treatment with a low-phenylalanine diet, these infants will develop mental retardation and behavioral problems. Other common symptoms of untreated classic PKU include seizures, developmental delay, and autism. Boys and girls who have classic PKU may also have eczema of the skin and lighter skin and hair than their family members who do not have PKU.
Babies born with less severe forms of PKU (moderate or mild PKU) may have a milder degree of mental retardation unless treated with the special diet. If the baby has only a very slight degree of PKU, often called mild hyperphenylalaninemia, there may be no problems and the special dietary treatment may not be needed.
PKU is usually diagnosed through newborn screening testing that is done shortly after birth on a blood sample (heel stick). However, PKU should be considered at any age in a person who has developmental delays or mental retardation. This is because, rarely, infants are missed by newborn screening programs.
PKU is treated by limiting the amount of protein (that contains phenylalanine) in the diet. Treatment also includes using special medical foods as well as special low-protein foods and taking vitamins and minerals. People who have PKU need to follow this diet for their lifetime. It is especially important for women who have PKU to follow the diet throughout their childbearing years.
PKU is inherited in families in an autosomal recessive pattern. Autosomal recessive inheritance means that a person has two copies of the gene that is altered. Usually, each parent of an individual who has PKU carries one copy of the altered gene. Since each parent also has a normal gene, they do not show signs or symptoms of PKU.
Gene alterations (mutations) in the PAH gene cause PKU. Mutations in the PAH gene cause low levels of an enzyme called phenylalanine hydroxylase. These low levels mean that phenylalanine from a person's diet cannot be metabolized (changed), so it builds up to toxic levels in the bloodstream and body. Having too much phenylalanine can cause brain damage unless diet treatment is started.
Currently, NHGRI is not conducting clinical research on PKU. However, studies are currently underway [clinicaltrials.gov] in other institutes within the National Institutes of Health.
Last Updated: January 2, 2019