Journal Articles

What is phenylketonuria?

Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the amount of the amino acid phenylalanine to harmful levels in the blood. (Amino acids are the building blocks of proteins.) If PKU is not treated, excess phenylalanine can cause mental retardation and other serious health problems.

Phenylketonuria is a subtype of hyperphenylalaninemia.

The signs and symptoms of this disorder vary from mild to very severe. The most severe form of the disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent mental retardation and behavioral problems. Seizures, delayed development, and movement disorders are also common. Many children have a musty or "mouse-like" odor as a side effect of too much phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members, because phenylalanine is important for skin pigmentation. Children with the disorder are also likely to have skin disorders such as eczema.

Less severe forms of PKU (sometimes called moderate or mild PKU) have a smaller risk of brain damage. People with very mild cases may not require treatment with a special diet.

Babies born to mothers with high levels of phenylalanine have a high risk of mental retardation because they are exposed to very high levels of phenylalanine before birth. These infants may also grow more slowly than other children and may have heart defects or other heart problems, small head size (microcephaly), and behavioral problems. Affected women with uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.

How common is phenylketonuria?

PKU is found in about 1 in 10,000 Caucasian (white) newborns. The disorder occurs much less frequently in infants of Japanese, Ashkenazi Jewish, Finnish, and African backgrounds. PKU is most common in Turkey, where 1 in 2,600 newborns is affected.

What genes are related to phenylketonuria?

Mutations in the PAH gene cause phenylketonuria.

PAH produces an enzyme called phenylalanine hydroxylase, which converts the amino acid phenylalanine to other essential compounds in the body. Normal levels of phenylalanine are important for brain function. This amino acid is found in all proteins and in some artificial sweeteners. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet can build up to dangerous levels in the bloodstream and other tissues. Excess phenylalanine damages nerve cells, resulting in brain damage.

How do people inherit phenylketonuria?

PKU is inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

What other names do people use for phenylketonuria?

Classical Phenylketonuria
Deficiency Disease, Phenylalanine Hydroxylase
Folling Disease
Phenylalanine Hydroxylase Deficiency Disease
Phenylketonuria I
PKU
Source: Genetics Home Reference, National Library of Medicine, National Institutes of Health

Phenylketonuria

Phenylketonuria (PKU) is an inherited error of metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase. Loss of this enzyme results in mental retardation, organ damage, unusual posture and can, in cases of maternal PKU, severely compromise pregnancy.

Classical PKU is an autosomal recessive disorder, caused by mutations in both alleles of the gene for phenylalanine hydroxylase (PAH), found on chromosome 12. In the body, phenylalanine hydroxylase converts the amino acid phenylalanine to tyrosine, another amino acid. Mutations in both copies of the gene for PAH means that the enzyme is inactive or is less efficient, and the concentration of phenylalanine in the body can build up to toxic levels. In some cases, mutations in PAH will result in a phenotypically mild form of PKU called hyperphenylalanemia. Both diseases are the result of a variety of mutations in the PAH locus; in those cases where a patient is heterozygous for two mutations of PAH (ie each copy of the gene has a different mutation), the milder mutation will predominate.

A form of PKU has been discovered in mice, and these model organisms are helping us to better understand the disease, and find treatments against it. With careful dietary supervision, children born with PKU can lead normal lives, and mothers who have the disease can produce healthy children.

What is phenylketonuria (PKU)?
Phenylalanine is an essential amino acid, which means the body must have it to grow and function properly. Too much can be harmful, so the body uses the enzyme phenylalanine hydroxylase to convert it into tyrosine.

In PKU, levels of this enzyme are low. This means only limited amounts if phenylalanine can be converted into tyrosine. As a result, phenylalanine build ups in the blood and other body tissues, particularly the brain, where it can cause severe and irreversible damage.

Symptoms
If PKU isn't detected early, progressive developmental delay and severe learning difficulties can occur. Other problems may include epilepsy and eczema.

Children with PKU typically have very fair hair and their urine has a musty smell.

PKU affects about one in 10,000 people. Classic PKU and several less common variants are all inherited in an autosomal recessive fashion, meaning that if both parents are carriers, each child has a 1 in 4 chance of having the disease. The PKU gene is found on chromosome 12.

All newborn babies are screened for PKU using a heel-prick blood sample. Antenatal screening is also available

Treatment and recovery
There's no cure for PKU but starting a low-phenylalanine diet as soon as possible after birth can help to avoid the harmful effects.

Phenylalanine is found in many proteins, so protein-rich foods such as meat must be avoided and replaced with 'safe' proteins, usually in the form of specially formulated substitutes. This diet should be followed in the long term.

Women with PKU must follow this diet while pregnant or they risk exposing their unborn children to high levels of the amino acid. This can lead to miscarriage, birth defects and brain damage, even if the children don't inherit PKU themselves.

Definition
Phenylketonuria (fen-ul-ke-to-NU-re-uh) is a birth defect in which a mutation occurs in a gene containing instructions for making the enzyme needed to break down the amino acid phenylalanine.

Amino acids are the building blocks for protein, and too much phenylalanine can cause a variety of health problems. People with phenylketonuria — babies, children and adults — need to follow a diet that limits phenylalanine, which is found mostly in high-protein foods.

Babies in the United States and many other countries are screened for phenylketonuria soon after birth. Although phenylketonuria is rare, recognizing phenylketonuria right away can help prevent serious health problems.